SPECIAL NUCLEAR MEDICINE€¦ · 4 medical and pharmacological advances 6 nuclear medicine, a...

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JANUARY 2015VOL 9 • NO 1

SPECIALNUCLEAR

MEDICINE

MEDICAL AND PHARMACOLOGICAL ADVANCES

4 MEDICAL AND PHARMACOLOGICAL ADVANCES

6 NUCLEAR MEDICINE, A DAY-TO-DAY MEDICAL SPECIALTY AND ITS CHALLENGES

7 CANADIAN NUCLEAR MEDICINE IN THE 21ST CENTURY

8 INTERVIEW WITH DR ALP NOTGHI, PRESIDENT OF THE BRITISH NUCLEAR

MEDICINE SOCIETY

9 INTERVIEW WITH PROFESSOR WEI HE, M.D. PH.D.

DIRECTOR OF NUCLEAR MEDICINEDEPARTMENT AND PET/CT

CENTER FU DAN UNIVERSITY, AFFILIATED WITH SHANGHAI HUA DONG HOSPITAL

10 THE USE OF PET IN NUCLEAR MEDICINE AND ITS SHAMEFUL LIMITATIONS OF ACCESS IN CANADA

11 NUCLEAR MEDICINE TECHNOLOGY TODAY ANDTHE ROLE OF THE TECHNOLOGIST

12 FRACTURES, A DIFFERENT APPROACH: THE ROLE OF EARLY BONE SCANNING

14 STATUS OF NUCLEAR MEDICINE IN ONTARIO

15 POSITRON EMISSION TOMOGRAPHY (PET)

22 NUCLEAR MEDICINE IN THE DIAGNOSIS OF HEART DISEASE

28 CLINICAL APPLICATIONS OF RADIONUCLIDE VENTRICULOGRAPHY

32 DATSCAN FOR DIAGNOSING PARKINSON’S DISEASE AND DEMENTIA WITH LEWY BODIES (DLB)

34 NUCLEAR MEDICINE IN THE DIAGNOSIS OF OSTEOMYELITIS

36 LOWER GASTROINTESTINAL BLEED:A FOCUS ON RADIONUCLIDE SCINTIGRAPHY

40 BRAIN IMAGING IN NUCLEAR MEDICINE

42 V/Q SPECT IN PULMONARYEMBOLISM

45 SCINTIMAMMOGRAPHY AND CANCER OF THE BREAST

SUMMARY

LE PATIENT Vol. 9, nº 1 3

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The cell becomes radioactive and the emitted raysare captured by an external PET camera. Powerfulcomputers interfacing with the PET camera identifyabnormal areas of radiation emission, a sign of theabnormal accumulation of F-18 FDG in the cancer-ous tissue.

The cancer tumour is detected and its activity ismeasured. Then a 3-D reconstruction is done, inmultiple slices and dynamically. The result is anexploratory metabolic autopsy of the patient in vivothat is non-invasive.

The external shape of the PET camera’s detectorresembles a tomodensitometer or magnetic reso-nance imaging device, but its function is complete-ly different. The other two devices produce mainlyanatomical images of the organs of the humanbody.

Moreover, today PET cameras are being teamed upwith tomodensitometry detectors and, in the nearfuture, will also be paired with magnetic resonanceimaging devices in order to better localize the site ofpathological processes.

With a simple intravenous injection of F-18 FDGthat is painless and without identifiable side effects,we are pushing the diagnostic limits ever furtherand tracking down cancer cells in their very last cel-lular bastions.

While F-18 FDG is currently the most commonlyused radioactive tracer, it is not the only one.Carbon-11, oxygen-15 and nitrogen-13, for exam-ple, can also be used to conduct neurological, car-diac or pulmonary exams.

In Quebec, PET technology is currently available insome nuclear medicine units. In mid-2008, thanksto new facilities in such places as Montréal, QuebecCity, Chicoutimi, Gatineau, Rimouski and Trois-Rivières, this newly deployed technology enabled

patients in centres that were not equipped withthese cameras to have access to PET scans within areasonable timeframe.

There are no inter-hospital charges or costs foreither hospitalized patients or outpatients. The costof each PET scan performed in a hospital centre isindividually, directly and completely covered by theGovernment of Quebec. PET scans are prioritizedbased on a patient’s clinical condition, whatever andwherever that may be, and not on the patient’sphysical location or the physical location of the PETcamera.

Considering that PET technology has been appliedas a just and universal social measure for all patientsin Quebec, this is a success story and an example tofollow.

ANTIMATTER AT THE SERVICE OF NUCLEAR MEDICINE

We can now measure and visualize the metabolicactivity of an organ in a human being and detect itsfunctioning and integrity. This is positron emissiontomography (PET) or, expressed another way, thefunctional imaging of cell metabolism.

Using PET, we can detect certain pathologies, suchas cancer, which initially alter the normal physiologyof cells.

In order to live, function and reproduce, the organ-ism’s normal cells need energy in the form of glu-cose (a sugar that can be metabolized by the organ-ism.) This energy source is indispensable to all theliving cells of the organism, and this sugar is foundnaturally in the blood. The more active a cell is, themore sugar it consumes.

A cancer cell that has lost all control over its unbri-dled multiplication must constantly consume largequantities of energy in the form of glucose (sugar).

In nuclear medicine, a glucose analog, deoxyglu-cose, is used as a decoy: it mimics glucose by enter-ing cells but in a form that cannot be used as anenergy source by the cancer cell.

To detect intracellular deoxyglucose, the molecule isradioactively labelled beforehand with a positron(antimatter) in the form of fluoride-18 (F-18).

As it accumulates in cancer cells, the positive elec-trons (e+) of F-18 come almost immediately in con-tact with the cell’s negative electrons (e-). This pro-duces a disappearance of the injected matter andantimatter, an annihilation reaction in which twophotons are emitted at 180 degrees in the form ofexternal radiation.

François Lamoureux,M.D., M. Sc.

PRESIDENT OF THE QUEBECASSOCIATION OF NUCLEAR

MEDICINE SPECIALISTS

4 LE PATIENT Vol. 9, nº 1

« The surgeonbecomes a robotic

manipulatorwhose movements

are measured inmillimetre preci-

sion. Roboticarms extend thesurgeon’s hand.Integrated cam-

eras magnifyvision by more

than 15x. »

MEDICAL AND PHARMACOLOGICAL ADVANCES

« With a simpleintravenous injec-tion of F-18 FDGthat is painlessand without iden-tifiable sideeffects, we arepushing the diag-nostic limits everfurther andtracking downcancer cells intheir very last cel-lular bastions. »


Nuclear Medicine is the medical specialtyinvolved in the diagnostic and therapeutic useof radioactive substances. We are one of the

29 medical specialties recognized by the RoyalCollege of Physicians of Canada and we form animportant part of both the imaging and therapyteam in most Canadian hospitals. Nuclear Medicine’sunique advantage resides in its ability to image andevaluate the various metabolic processes occurring inthe human body, in a non-invasive and dynamicmode (as they happen in real time, often over sever-al minutes and sometimes hours). This gives us anexceptional access to most physiologic and diseaseprocesses and opens the door to what we believe isthe future of medicine: metabolic and personalizedmedicine. The rapid development of hybrid imagingdevices (combining Nuclear Medicine conventionalcameras and PET scanners with CT scanners) hasbrought the benefits of precise localisation andanatomic characterization to traditional NuclearMedicine, making it much more powerful.

We nevertheless face serious challenges, very muchlike the rest of the medical community. With fewerfunds available for health care, the development ofimaging technology is continuously being ques-tioned and we must strive to keep our just place in

the medical team. The delay in the deployment ofPositron Emission Tomography (PET Scans) in Ontariois a good example of it. The regulatory environmentregarding the approval of radiopharmaceuticals inCanada (the products used in Nuclear Medicine pro-cedures) must not unduly retard their adoption in ourdepartments, so that Canadians are allowed worldclass access to newer imaging drugs. Finally, Canadamust seriously consider the safety of itsMolybdenum/Technecium supply (the main productsused in Nuclear Medicine departments) as it preparesto close down its NRU reactor in Ontario (one of theworld’s most important sources of medical isotopes).

It is our profound belief that progress in radiophar-maceuticals and imaging technology will continue toensure a bright future to our specialty. The quality ofNuclear Medicine in Canada is the envy of much ofthe rest of the world. Canadians do not like to bragabout themselves generally, but in the case ofNuclear Medicine and the peaceful use of atomicenergy, they should. After all, Canada was the firstcountry in the world to recognize Nuclear Medicineas a medical specialty, and we were (and still are)world leaders in the production of medical isotopesand nuclear reactors for peaceful use.

Dr Norman LaurinM.D., FRCPPRESIDENT:CANADIAN

ASSOCIATION OFNUCLEAR MEDICINE

2012-2014

NUCLEAR MEDICINE,A DAY-TO-DAY MEDICAL SPECIALTY AND ITS CHALLENGES


Dr Andrew RossPresident, CanadianAssociation of NuclearMedicine

CANADIAN NUCLEAR MEDICINEIN THE 21ST CENTURY

It was the best of times; it was the worst of times.This adage can well be applied to Canadian NuclearMedicine practice in the early 21st century. New tech-

nology and the promise of exciting tracers to diagnoseillness and therapies abound. Nuclear Medicine playsan integral role in investigation and treatment ofpatients. However, jeopardy in terms of regulations,healthcare economics and isotope supply work totemper the excitement. The challenge for those withknowledge of the potential is to be active and proac-tive to capture as much of the positive as possible.

The deployment over the last decade of the advancedSPECT/CT and PET/CT imaging cameras, which accu-rately show changes in physiology caused by diseaseslinked with the anatomy has enhanced the relevanceand importance of Nuclear Medicine, expanding itsscope within diagnostic medicine. PET in particular hasseen exponential growth. After a slow deployment(outside Québec), virtually all provinces now possess orhave access to, and have recognized this importantdiagnostic tool. However, many jurisdictions place lim-itations to access.

The growth has almost entirely been fuelled by FDG,radioactive labeled sugar. Its power to diagnose andprovide important information about cancer has revo-lutionized how this disease is investigated. It can alsoprovide important information in certain patients withheart disease and brain disorders. There are manyother promising tracers used elsewhere such asradioactive dopamine which has use in difficult tomanage cancers and amyloid agents which can pro-vide vital information to help manage some patientswith dementia.

Radiolabelled therapeutic agents have seen some lim-ited utilization in Canada, but this lags other countries.Much of this relates to regulatory issues and the rela-tive small market Canada represents, which decreases

the initiative of companies to pursue efforts for usehere. Agents such as alpha emitters for bone metasta-sis and other agents in neuroendocrine cancer showgreat promise for treatment. Working together, wecan hopefully obtain expanded access for Canadianpatients to these important therapies.

A challenge to overcome is the regulatory burdenplaced on tracer approval. This will continue to be oneof the most important issues to provide access. Otherjurisdictions, notably Europe, are more advanced inthis regard. It is paramount we continue to educatethe regulators to recognize the unique status of radio-pharmaceuticals. Currently, they fall under the full reg-ulatory burden of drugs. This equates the minutedoses of near physiologic molecules labelled with fastdecaying tracers used in Nuclear Medicine to mass dis-tributed therapeutic agents from large pharmaceuticalcompanies. It is important to provide safe, well stud-ied agents. However meeting the current regulationsis not only challenging but highly expensive for thesespecial agents.

The other major jeopardy for Nuclear Medicine is the“made in Canada” problem involving supply of ourworkhorse medical isotope, 99-Technetium. In 2016,closure of the Chalk River reactor, which is the onlyNorth American producer, will precipitate a highlyjeopardized supply chain causing price escalation andpotential shortages.

Nuclear Medicine has and continues to be a vitalcontributor to patient care. There is a dedicatedteam of professionals including doctors, technolo-gists, radiopharmaceutical scientists and a support-ing industry. There is a bright future with muchopportunity to further enhance this vital work. It isimportant that all who understand or have beentouched by it, work to help overcome the challengesto its continued success.


1. British medicine has always been one of the most advanced in the world. What is the situationof nuclear medicine?

Nuclear medicine has always been one of the smallest spe-cialities in medicine. However, in the UK, because of itsmultidisciplinary nature and close association with physicsand radio-pharmacy, it has always attracted people withbroader interests beyond just medicine, and usually scien-tifically-minded, often from all over the world. This hashelped to maintain its niche in the forefront of advancesin nuclear medicine worldwide.

2. Is nuclear medicine accessible all over UnitedKingdom?

There are over 200 hospitals with nuclear medicine servic-es in the UK. Some are dedicated nuclear medicine depart-ments which are involved in research and development,mostly in larger hospitals and also deliver the more spe-cialised investigations and therapies, whilst other depart-ments deliver only the more common NM procedures,making these accessible for most of the UK population.

3. How many centres have Positron EmissionTechnology (PET)? And how many future PET centres will there be in the next five years?

PET facilities are mostly associated with cancer care centres(cancer hobs for each region) or are research based (all

together, 63 PET cameras in the UK). However, there is aneed for expansion in the services and with the recogni-tion of developments in non-cancer applications of PET,there are plans to expand this to more centres and makeit routinely available for more hospitals, as local expertiseand local one-to-one discussion of cases with referrers(MDT meetings) are recognised to be as important as thetest itself.

4. How is training done for nuclear medicine specialists and technologists?

Nuclear medicine training is one of the Royal College ofPhysicians specialities. However, with integration of hybridimaging for attenuation correction, localisation and now,diagnostic scanners, we have developed a program toinclude an initial 3 years training in radiology (culminatingin fellowship of the Royal College of Radiologists), fol-lowed by 3 years nuclear medicine training (including aminimum of university diploma in nuclear medicine); stillremaining a RCP speciality. Technologist training is a sepa-rate training scheme from radiographers. However, closerintegration may be necessary as an increasing number ofhybrid cameras have diagnostic CT.

5. Nuclear medicine is expanding worldwide. How do you share your expertise with colleaguesof other countries, and especially in Canada?

I see closer links between the British Nuclear MedicineSociety with sister societies and organisations such asCanadian Association of Nuclear Medicine as a positivestep which brings together the expertise developed whichwould have mutual benefit for the countries.

6. Where do you think nuclear medicine is going inthe near future, and what should nuclear medicinespecialists do next?

There are exciting developments with new tracers (inparticular PET) and therapy which will expand the role ofNM. New camera technology with increasing resolutionand sensitivity has meant faster patient throughput,reduced radiation and better images, increasing theappeal of NM as a diagnostic modality. Better integrationof hybrid technology (diagnostic CT and MRI) has meantwe should rethink the patient pathways, reducing thenumber of patient visits and delays in diagnosis, givingmore accurate diagnoses by combining the informationfrom different modalities. There is a strong case fordevelopment of more SPECT agents as well as PET agentsas the availability of SPECT is more universal, and in gen-eral costs of tests are lower.

7. Finally, what is your best wish for nuclear medicine?

To successfully integrate new developments into nuclearmedicine whilst remaining a strong independent specialityand providing unique molecular and physio-pathologicalinformation, thus helping to understand and alter diseaseprocesses, therefore improving patient care.


INTERVIEW WITH

DR ALP NOTGHI PRESIDENT OF THE BRITISH

NUCLEAR MEDICINE SOCIETY

1. China is the most populated country in the world and amongst the most powerfulcountries in the world. Professor He, you arepersonally one of the most influential Chineseleaders in medicine. What is the situation ofnuclear medicine in China?

We are at the early stages of deployment of nuclearmedicine. Our central government recognizes thepower of nuclear medicine and, consequently, is verysupportive. As we need better diagnostic tools, wehave the chance to rapidly get the state of the artequipment in a cost effective perspective. So all theexisting and new nuclear medicine departmentshave, or will have, at least the most modernSPECT/CT and many departments also the PET/CT.Only a few university centers will get the PET-NMRtechnology, mostly for research purposes.

2. How many centers are there in China at thepresent time?

Approximately 1000 SPECT/CT units and 250 PET/CTunits. More than 98% are independent nuclear med-icine departments under the responsibility of nuclearmedicine specialists.

3. How many new nuclear medicine centers doyou think will open in the next three years?

I think approximately 400.

4. How is training done in China for doctorsand technologists?

At the moment, only two universities offer a trainingprogram and our residents acquire additional expertisethrough other international nuclear medicine pro-grams. There is a need to further develop this aspect inour training programs. For our technologists, there isnot actually a formal training program. Most of theexpertise is acquired locally. This also is a field that weneed to look to develop partnerships with other coun-tries, like Canada for example, where you have wellrecognized technologist schools in nuclear medicine.

5. Nuclear medicine is expanding rapidly worldwide. How do you keep in touch, shareyour expertise and develop new nuclear medicine applications with, for example, your Canadian colleagues?

Today, the world gets smaller. So we participate inmany international meetings, we offer our youngdoctors the possibility of going abroad for additionalfellowships and we believe in exchanges of visitingdoctors. We also use the e-journals and e-training alot. For example, in my department in Shanghai, wehave the Hermes platform and through it we use theCLOUD to easily exchange and access training mate-rial, so we can adopt it for China. We have alreadyclose links with our Canadian colleagues and we arelooking to increase it in the near future, either for ourtechnologists or for our doctors and vice versa.

6. For many all over the world, Shanghai is theexample of a city of the future. What is the situation of nuclear medicine in Shanghai?

Shanghai and Beijing are the two leading cities withgood economic situations. We have very well educat-ed staff and we have many channels to the world.Our young specialists travel the world and bring backthe best for our nuclear medicine departments. Also,almost all of them master the English language.

7. Finally, Professor He, what is your greatestwish for China and Canada regarding nuclearmedicine?

As China and Canada share the same vision ofnuclear medicine, as in fact the molecular specialityof today, I long to share more our mutual expertise,our knowledge. So in our day to day work, ourpatients could benefit rapidly from the contributionof nuclear medicine and its molecular power to diag-nose diseases earlier, and also offer them rapidly themost appropriate treatments that nuclear medicinebrings also to the patient in many situations. Canadaand China have so much in common that we couldeasily share what each of us has, the best in clinicalguidelines, training programs and research.

INTERVIEW WITH

PROFESSOR WEI HEM.D. PH.D.DIRECTOR OF NUCLEAR MEDICINEDEPARTMENT AND PET/CT CENTERFU DAN UNIVERSITY, AFFILIATED WITHSHANGHAI HUA DONG HOSPITAL


Jean-Luc Urbain, M.D., Ph.D., CPE

Past President,Canadian Association

of Nuclear Medicine

Jean-Noël Talbot, M.D., Ph.D.

Professor at Pierre andMarie Curie University

(Paris), Past President, Île-de-France Association of

Nuclear Medicine


The very basis of Diagnostic Nuclear Medicineconsists in its unique ability to trace, thanks to avery minute amount of radioactivity, the very

same molecules that the human body processes tocarry out all living tasks. This unique approach enablesnon-invasive imaging to evaluate the physiology andpathophysiology of our tissues and organs. The quin-tessence of the added value of nuclear medicine tomedical diagnosing is nicely illustrated by PositronEmission Tomography (PET), the most recent modalityin clinical non-invasive imaging.

Introduced in the late 50s, PET has, nowadays,evolved into a critical clinical diagnostic tool for themanagement of patients with cancer, inflammatory,cardiac or neurological diseases. Coupled with theanatomic definition of Computerized TomographyScanners or Magnetic Resonance Imaging, PET/CT andPET/MRI are the ultimate clinical imaging instrumentsto detect, pinpoint, characterize, quantify, manageand follow the vast majority of diseases afflictinghuman beings at the molecular level.

Over the past three decades, there has been a vastarray of medical positron emitting isotope compoundsthat have been synthesized and tested for the imagingand quantification of cell receptors, metabolic and sig-naling pathways using PET.

In 2012, approximately 2.5 million PET procedureswere performed in the US. The main application ofPET has been and remains the tracing and quantifica-tion of glucose metabolism using 18F-FDG, a mole-cule of glucose labeled with a radioactive fluorine.18F-FDG, PET/CT or PET/MRI has become the tool ofchoice for diagnosing, staging, prognosing, monitor-ing and following up patients with cancer, since thecancer lesions usually display an increased glucosemetabolism. FDG PET is also useful for detecting, atthe whole-body level, unknown infectious or inflam-matory foci. In addition, three other oncology PETtracers have also been registered in France and in sev-eral EU Member States for imaging prostate or pri-mary liver cancer (fluorocholine), neuroendocrine orbrain tumours (FDOPA) or skeletal malignancies (fluo-ride). Furthermore, very active research programs todevelop PET tracers of apoptosis, tumour angiogene-sis and biomarkers for imaging breast cancer, prostatecancer, melanoma, colorectal cancer and renal cancerwill expand diagnostic options and enable personal-ized targeted therapies.

While 18F-FDG PET represents about 90% of the clin-ical PET procedures, increasing by 10% per year, car-diac PET studies using rubidium now represent 10%of the PET studies. Over the past two decades, rubid-ium has indeed provided the cardiologists with a very

effective tool to diagnose complex cardiac diseaseswith increased confidence and to select the patientswho will benefit most from revascularization. Thedevelopment of PET cardiac tracers for the imaging ofperfusion and the vulnerable plaque will furtherincrease the functional value of PET by providingmolecular information on acute coronary syndrome,cardiac heart failure and offering more effective pre-ventive and treating approaches.

In the neurology field, a recent breakthrough hascome for the FDA approval of Amyvid (Eli Lilly),Vizamyl (GE) and more recently, NeuraCeq (Piramal),the new PET biomarkers for early imaging of amyloidsubstance deposition leading to Alzheimer’s disease.

Unfortunately, PET programs in the English part ofCanada are still largely underdeveloped compared tothe US, Europe and now Asia. Besides the Province ofQuebec, where PET scintigraphy has flourished overthe past decade, the implementation of clinical PET inthe rest of Canada, particularly in Ontario, has beenmarred by severe restrictions by the provincial govern-ments. While both Quebec and Ile de France (Parisregion) performed about 50,000 PET procedures peryear for a population of ca. 9 million, only 12,500 PETscans have benefited the 13 million Ontarians. Basedon conservative estimates derived from cancer reg-istries and the incidence and prevalence of the varioustypes of cancers affecting Canadians, it is estimatedthat Canada should perform between 200,000 and250,000 oncology PET studies per year.

We sincerely hope that the article published in thismagazine by Éric Turcotte from Sherbrooke on theindications of PET will encourage the health careauthorities across Canada to finally provide its citizenswith 21st century PET access.

The Canadian Association of Medical RadiationTechnologists (CAMRT) is the national profes-sional association and certifying body for 12,000

radiological, nuclear medicine and magnetic reso-nance imaging technologists and radiation therapists(MRTs). CAMRT offers a suite of programs and servic-es that advance the profession and the health ofCanadians, and is the authoritative voice on issuesthat affect its members. 1,350 of these are nuclearmedicine technologists.

Nuclear medicine procedures involve the applicationof radiopharmaceuticals in the diagnosis and treat-ment of disease. Nuclear medicine has beendescribed as "radiology done inside out" because itrecords radiation emitting from within the bodyrather than radiation that is generated by externalsources like X-rays.

Nuclear medicine scans are conducted by a certifiednuclear medicine technologist (MRT). To become acertified technologist, one must first complete anundergraduate education program that is accreditedby the Canadian Medical Association. The MRT pro-vides the essential link between the sophisticatedtechnology and compassionate patient care. In thecourse of performing their work, their expertise isapplied to administering radioactive chemical com-pounds, known as radiopharmaceuticals, and per-forming patient imaging procedures using sophisti-cated radiation-detecting instrumentation. They alsocarry out the computer processing and imageenhancement before providing images, data analysis,and patient information to the physician for diagnos-tic interpretation.

During an imaging procedure, the technologist isresponsible for patient care. Not only do they obtainpertinent history, describe the procedure and answer

any questions but they also closely monitor thepatient's physical condition during the course of theprocedure.

CHALLENGES AND OPPORTUNITIES OF THE FUTURE

Over the past few decades there have been excitingnew developments in the field of nuclear medicine.Positron emission tomography (PET) has gained broadadoption. It uses very short life isotopes that are pro-duced in cyclotrons. PET imaging is very sensitive andallows the visualization of functional processes in thebody. It is used mainly in clinical oncology and neu-roimaging. PET scanners are now often combinedwith CTs (PET-CT) and MRIs (PET-MR) to produce highquality anatomic and metabolic information. InCanada, the adoption of PET imaging has beenslowed by the limited number of cyclotrons and thehigh cost of the procedures.

Single-photon emission computed tomography(SPECT) on the other hand is highly dependent onreactor produced medical isotopes. 2 of the 9 reac-tors used in the supply chain are scheduled to stopproduction in 2016 (including the Canadian NRU atAtomic Energy Canada Limited, Chalk River, and theFrench OSIRIS reactors). Together, these reactorsaccount for about 25% of the current worldwideannual production volume. Other major existingproducing reactors, except for OPAL in Australia, areaging and scheduled to shut down by 2030. Thereare many projects under way around the world tocreate alternative sources of supply. The Canadiangovernment, for example, has invested over $35 mil-lion in research and development of innovative newapproaches that involve the use of cyclotron technol-ogy to produce technetium-99m, an isotope used for80 per cent of nuclear medicine diagnostic proce-dures. However, at this time, it is uncertain as towhether these projects will be fully operational ontime to ensure a steady and reliable supply when thereactors close.

The CAMRT is monitoring the situation and coordi-nating ongoing investigation through dialogue andinformation sharing with CAMRT members, interna-tional colleagues and other national healthcare asso-ciations. Discussions are ongoing, with HealthCanada, with provincial and territorial governmentrepresentatives, and various industry players. Thegoal is to monitor the situation closely and stimulatethe emergence of mitigation strategies that willensure little or no disruption to Canadian patientswho require a nuclear medicine scan.

THE USE OF PET IN NUCLEARMEDICINE AND ITS SHAMEFUL LIMITATIONS OF ACCESS IN CANADA


NUCLEAR MEDICINETECHNOLOGY TODAY AND THEROLE OF THE TECHNOLOGIST

François Couillard, B. Eng, MBA, CMC, CEO of the CanadianAssociation of MedicalRadiation Technologists(CAMRT)

FRACTURESA DIFFERENT APPROACH: THE ROLE OF EARLY BONE SCANNING


Christopher O’BrienMDCM; FRCPC

Medical Director, NuclearMedicine

Brantford General Hospital

achieved by 48hours after theevent. Up to 72hours post eventmay be requiredfor the severelyo s t e o p e n i cpatient.

A bone scan canbe tailored toassess a specificsite only (e.g.the hand orfoot) or a moreregional assessment (e.g. the pelvis and lowerextremities). At times a whole bone assessment maybe required, especially in cases of more severe trau-ma. By tailoring the study, one can assess both thearea of discomfort and also have the ability to assessfor referred pain from occult fractures elsewhere.

It is important to realize that there is no increase inradiation exposure as one takes more images, as theradiation exposure comes from the injection. Theaddition of SPECT does not add any more radiationeither as this is a simple 3-dimensional reconstructiontechnique. SPECT/CT, however, does add a very smallamount of extra exposure linked to the CT, but a lowdose technique is used to keep this exposure to aminimum.

PATIENT MANAGEMENT ISSUES

When a patient presents complaining of bone pain, itis important to obtain a history to assess for possiblepost-traumatic causes, perhaps insufficiency causes,or perhaps neoplastic causes. After the history and ifclinical indication exists, then the first imaging is usu-ally plain film X-ray of the area of discomfort. If X-rays are obtained very shortly after the event, thesensitivity is low: 10 to 15% (especially with stressfractures and in those individuals with low bone den-sity), and it may take up to two weeks or more beforechanges become more apparent with plain film X-ray.Thus there is the need for a follow-up X-ray if clinicalsymptoms persist.

However, even with this we see many patients pre-senting to Nuclear Medicine to obtain a bone scan toassess the possibility of fracture, even one monthafter the event because X-rays are still normal orinconclusive, and because of this the patient may nothave received optimal clinical care.

To maximize patient care, one could consider a bonescan as the next imaging technique if initial X-rays arenormal and clinical symptoms remain. Thus, onecould consider performing a bone scan much earlierin the work-up of the patient due to its very high sen-sitivity which rivals MRI (sensitivity of 85 to 95%).

If referring physicians begin to request bone scanningearlier after initially negative X-rays in order to opti-

mize patient management, then it will be necessaryfor the Nuclear Medicine department to establish arapid response process to fast track patients with sus-pected fractures. If the waiting time is 2 to 3 weeks,this does not do the patient any good. In addition,the Canadian Medical Association Wait Time Alliancehas suggested that urgent cases (which include frac-tures) should obtain a bone scan within one week ofthe request and preferably within around 48 hours ofthe request, in ideal situations.

I believe that by following this approach, the diagno-sis of fractures will be made quicker, patients canthen be referred for appropriate management soon-er, and the patient will be able to return to routineactivities of daily life and will also have better paincontrol.

In conclusion, the routine bone scan is a safe andhighly sensitive technique (98% at one week) andwith the addition of SPECT/CT, it now has high speci-ficity as well. It should be considered as the nextimaging technique if X-rays are normal and clinicalsymptoms persist one week after the initial X-rays. Inaddition, the Nuclear Medicine departments will haveto set up a process to fast track these requests inorder to optimize patient care.


The three-phase bone scan is a very sensitivetechnique used in the detection of fractures ofany cause. The sensitivity can be further

increased through the use of SPECT and the specifici-ty can be improved by adding the technique ofSPECT/CT. The sensitivity ranges from 80% to 98%depending on when imaging is performed andwhether SPECT is used, or 24 hour delayed imaging

is obtained. Thus the sensitivity at 24 hours postevent is 80%, 95% by 72 hours and 98% by oneweek.

The reason that the sensitivity is lower with earlyimaging is that the osteoblasts must become activat-ed and it is osteoblastic activity that is assessed withthe bone scan. The higher sensitivity is usually

STATUS OF NUCLEAR MEDICINE IN ONTARIO


Christopher O’BrienNDCM FRCPC

President, OANM

Dear colleagues,

On behalf of the Ontario Association of NuclearMedicine (OANM), I wish to thank you for theopportunity to bring you this update. There aremany challenges faced by Nuclear Medicine inOntario that are not found in Quebec. There arealso benefits that aid patient access to Nuclearmedicine procedures, so all is not gloom!

CHALLENGES

1. Physician Qualifications

In Ontario, Royal College Certification in a specificspeciality is not required in order to practice that spe-ciality. Although there are around 150 physicianspracticing Nuclear medicine in Ontario, only approxi-mately 60 of these are actually certified as NuclearMedicine Specialists by the Royal College. Many ofthese are dual certified either in NuclearMedicine/Internal Medicine or NuclearMedicine/Radiology. The OANM believes that thisbrings strength to the speciality. However, we areconcerned that many physicians only have a fewmonths exposure to Nuclear Medicine during residen-cy training in Radiology, but yet they are allowed topractice full Nuclear Medicine if granted privileges bytheir hospitals. This is possible as neither the Collegeof Physicians and Surgeons of Ontario (CPSO) nor theMinistry of Health require speciality certification. Thelevel that these physicians are functioning at isunknown. In Quebec, Certification in NuclearMedicine is a requirement.

2. Positron Emission Tomography

It was only in October 2009 that the Government ofOntario allowed PET to become an insured procedurethrough OHIP. The indications for PET remain the

most restrictive in Canada: these can be foundthrough the following link: www.petscansontario.ca.

Initially, there was funding for only 2400 patients forthe entire province of Ontario (10 PET centers) com-pared to the 24,000 for Quebec. It is anticipated thatwithin the next year, funding will increase to 7000patients, still well below the Quebec numbers andwell below the numbers seen across Canada, thoughthe situation for Ontario patients is improvingthrough co-operative efforts between theGovernment and the Nuclear Medicine community.

3. Funding for Procedures

Quebec follows a global fee structure for operationalfunding for Nuclear Medicine services, whereasOntario follows a fee for service model, both forOperational (Technical fee: T Fee) and Professionalremuneration. In other words, the money follows thepatient. This has allowed the waiting lists for NuclearMedicine procedures to be very small, studies usuallydone within a week or two for non-urgent cases. InOntario, we usually do 8000 bone scans and around12,000 heart scans per month. Almost all of our hos-pital departments have SPECT/CT units, althoughnone of our non-hospital clinics (Independent HealthFacilities: IHFs) have any. This is due to difficulty inobtaining authorization to have a CT in non-hospitallocations and lack of funding for the CT componentof SPECT/CT procedures: Attenuation correction andImage Localization. These CTs are non-diagnostic.There is no private system in Ontario.

4. Medical Isotope Shortage

As in Quebec, the availability of medical isotopes hasbeen a challenge. Even with the present shortage, wehave been able continue to offer all services to all ofour patients when needed. This has been accom-plished through the efforts of the industry to sourceother suppliers of isotopes, technologists and clericalstaff in juggling schedules and coming in on week-ends, and to the physicians for taking a leadershiprole. This has come, however, at a significant increasein costs which have yet to be reimbursed by either thefederal or provincial governments, calling into ques-tion the sustainability of some of our departments,and subsequent patient access to required NuclearMedicine procedures.

Though both provinces face a different set of chal-lenges, the future does look bright for the speciality:new equipment and isotopes are becoming availablewhich will allow a more detailed assessment ofpatients at lower radiation exposures, as well as theincreased access to PET and new PET isotopes. Thiswill allow the unique information obtained throughNuclear Medicine procedures to continue to help youmanage your patients.

Positron Emission Tomography (PET) is a cuttingedge, non-invasive, diagnostic imaging tech-nique which allows the measurement of bio-

chemical processes or the expression of cellularreceptors by the use of positron-emitting radioactivetracers. The imaging tracers most often containatoms naturally found in organic molecules, but inthe form of radioactive analogues of Oxygen (15O),Nitrogen (13N), Carbon (11C) or Fluorine (18F) atoms.

Developed during the 70s to study the normal andpathological brain function, in the 90s, PET becamean important clinical tool for oncological imaging fol-lowing the demonstration of its usefulness in thedetection of several cancer types.

Initially confined to research centers, PET has spreadrapidly since 1998 to the vast majority of importantoncologic centers in industrialized countries. Since2001, PET has been paired to axial computed tomog-raphy (CT) (Figure 1) in order to better locate lesionsby relation to the anatomical structures. It also facili-tates the interpretation of results by improving thespecificity and, furthermore, combined PET/CT dataallows the planning of radiation therapy treatment.PET/CT images also have a considerable advantagefor planning the surgical approach, since an accurateanatomical localization may be established. It is alsopossible to merge any PET study to any three-dimen-sional imaging including MRI and SPECT tomogra-

phy, even if they have been obtained on differentdevices or at different times (Figure 2).

Gradually, the price of PET/CT devices has droppedby half and now can be purchased for 1.2M$. Thescanner allows the accomplishment of a full studyfrom the neck to the pelvis in less than 25 minutes,thus improving considerably the productivity of PETand helping to reduce the cost of each exam(throughput of 15-20 exams per scanner per 8hours). Since 2005, PET/CT technology deployedquickly in the public and the private health systemsacross Canada. However, in 2014, access to PET isvery different from east to west provinces andCanada is still behind many developed countries.Quebec is by far the province providing the bestaccess to this technology. Quebec is also the firstprovince which has deployed the latest generation ofPET/CT devices to regional hospitals away from aca-demic and research centers.

As with the studies performed in conventionalnuclear medicine (bone or thyroid scan, myocardialperfusion, etc.), PET/CT is performed after the intra-venous injection of a radioactive substance calledradiotracer. Over the past few years, several radio-tracers have been developed for the detection ofcancer and the most important is the fluorine-18Fluorodeoxyglucose (18F-FDG). The fluorine-18, witha half-life of 110 minutes, is the isotope of choice for

Eric Turcotte, MD, FRCPCNuclear MedicineSpecialistClinical Research Head of the Molecular ImagingCenter (CIMS)Associate Professor,University of Sherbrooke

POSITRON EMISSIONTOMOGRAPHY (PET)


can cause false positive results (Figure 7). Conversely,some well-differentiated cancers, such as prostatecancer, high mucinous content tumours, well differ-entiated neuroendocrine tumors, and certain lobularbreast cancers may have a low uptake. Others, suchas the hepatocarcinoma, possess phosphorylases,which allow cells to quickly eliminate the 18F-FDG. Alist of clinical indications for oncology PET with 18F-FDG is detailed in Tables 1 and 2. Taken together,lung cancer (Figure 8) and lymphoma indications rep-resent about 50% of the available imaging time on aPET scanner.

PET should be an accessible exam to be consideredby a specialist as well as the family physician.However, for a better management of the resource,it is important to recognize the strengths and weak-nesses of the technique in order to ensure that theexamination can answer the clinical and therapeuticdilemma. The following guiding points are to be con-sidered if a PET/CT exam is to be requested:

Does the patient need to be fasting? Is fastingmandatory for all patients? What about diabet-ic patients?

Patients arriving for their exam must obey the fastingprocedure (sugar-free) for at least 6 hours prior tothe exam. Diabetic patients can take their oral hypo-glycemic agents and their slow onset insulin dose inthe morning of the examination day. However, spe-cial attention should be paid to metformin becausethis medication is responsible for a very intensebowel uptake (Figure 9). Thus, metformin should bestopped at least two days prior to PET if an intestin-al lesion is suspected.

All sources of glucose (including lozenges, mints,gums, glucose in solution) must be strictly avoided soas to maintain circulating insulin at the basal level. Ifthere is any doubt about the patient’s glucose intakein the last six hours, the study should be deferred inorder to observe fasting procedure for at least sixhours (Figure 3). It is also required that the capillaryblood glucose level at the time of injection is lessthan 10 mmol/L. If the result is higher than 10mmol/L, one to two doses of rapid i.v. insulin can beinjected in order to normalize the blood glucoselevel. An additional waiting period of 60 minutes isnecessary to allow the exogenous insulin to bemetabolized. The exam will be postponed to a laterdate if it is not possible to normalize the blood glu-cose level. It is therefore important to ensure thatthe diabetes is well controlled and that the glucoselevel is normalized (or almost) and stable beforerequesting an 18F-FDG study.

Is there a reasonable doubt of neoplasia in respectto the clinical and para-clinical evaluation?

The prescription of an oncology PET study shouldideally be limited to patients with proven or strongly

suspected neoplasia. A clear clinical question shouldbe included in the request form for the exam. It is theresponsibility of the requesting physician to be asclear as possible.

cancer imaging. This isotope can easily be distributedto multiple institutions and its long half-life allows itto accumulate at levels that are sufficient for imagingwith adequate contrast for tumor detection. Themolecule of 18F-FDG is an analogue of glucoseobtained by substituting a hydroxyl (-OH) group of aglucose molecule by a radioactive fluorine atom witha nucleus that contains more protons than neutrons.This atypical ratio of protons/neutrons makes theatom unstable and the latter must expel a positivecharge in the form of a positron to regain its stabili-ty. The PET devices are conceived to detect radioac-tive emissions induced by these positrons, and to pre-cisely locate this emission inside the body. At the cel-lular level, the 18F-FDG uses the same transmembranecarriers as glucose, and its passage is transporter –and insulin – dependent. After its entry into the cell,the 18F-FDG is phosphorylated by the hexokinase, butit rapidly stops advancing into the glycolysis cascade.It thus becomes sequestered in the cell where it accu-mulates. The 18F-FDG permits to obtain cellular infor-mation relative to the cell viability and metabolismbased on the metabolic rate of the cellular glucose.

The excretion of 18F-FDG is mainly through the urinarytract, regardless of if the patient is diabetic or not,

because the 18F-FDG molecule is not completely reab-sorbed by the renal tubules, unlike glucose. There isalso a certain proportion, very variable from one indi-vidual to another, which is excreted by the intestines.Figure 3 (left) shows a normal biodistribution of 18F-FDG compared to the image on the right which illus-trates the important consumption of 18F-FDG by stri-ated muscle due to a non-respected fasting/glucose-free procedure. Figure 3 (right) is considered non-diagnostic. Consequently, the exam must be repeat-ed at a later date.

The 18F-FDG PET is aimed at four main fields of clini-cal application: oncology, cardiology (Figure 4), neu-rology (Figure 5) and infection/inflammation (Figure6). Overall, in a general hospital, more than 95 percent of the examinations currently carried out are foroncologic indications. The rationale behind the use of18F-FDG PET in oncology is based on the increased useof glucose by the neoplastic cells, a phenomenonclosely linked to the neoplastic transformation. A rap-idly growing neoplasia is also ischemic in its center,hence favoring the metabolic pathway of lactic acid,which greatly increases the demand for glucose. Anon-negligible proportion of the uptake also comesfrom the inflammatory cells surrounding the tumor. Itshould be noted, however, that these phenomenavary significantly depending on the type of neoplasia.

Although PET is excellent to detect neoplastic lesions,it has limitations. Some cancers have slower growthand do not substantially increase their 18F-FDG accu-mulation and may remain undetectable (false nega-tive). The activated neutrophils and macrophages canconsume a lot of glucose and the highly inflammato-ry lesions can also incorporate this radiotracer (falsepositive). In particular, active granulomatous inflam-mation (tuberculosis, sarcoidosis) as well as abscesses

Figure 1 : PET/CT scanner allowing to sequentially obtain an axial tomography (CT) and a positron emission tomography (PET) during a same medical visit.

Figure 2 :Current software which enables the merging of PET not only with the CT, but with all 3D imaging modalities, including MRI. PET-MRI fusion allows better localization and characterization of the neoplastic cerebral lesions (the arrow shows a voluminous pituitary prolactinoma).

Figure 3 :PET studies performed in two different patients. The imageon the left illustrates a normal biodistribution of FDG in apatient having observed the fasting procedure. The imageon the right has been obtained in a patient with dextrose

solute (diffuse muscle uptake induced by hyperinsulinemia).

Figure 4 :This PET exam uses ammonium to assess myocardial perfusion

at rest and FDG for viability. This exam is more sensitive thanThallium for the demonstration of severely ischemic regions at

rest or hibernating myocardium in order to orient the therapeutic approach (to increase the ejection fraction and

decrease morbidity). The example illustrates severe hypoperfusion at rest (rest ischemia) in the region of thedescending anterior, completely viable on the FDG study. The study therefore suggests that this wall will resume a

normal kinetic after revascularisation that will result in gain of ejection fraction.

Figure 5 :Brain FDG PET in search of inter-ictal epilepsyfoyers. Right temporal hypometabolism testifiesto an epileptic foyer (arrow).

Table 1:

• Characterization of a mass: benign versus malignant

• Evaluation of the extension of the disease (staging and restaging)

• Orientation toward the most accessible biopsy site

• Detection of occult primary tumor site in patients with metastatic disease

• Detection of residual disease after chemotherapy/radiotherapy or surgery

• Radiotherapy planning (delineation of gross-tumor-volume)

• Differentiation between relapse and post-surgical/post-radiotherapy changes

• Biochemical evidence of relapse (elevated markers) without clinical signs or radiological evidences

• Follow-up or surveillance when conventional studies are equivocal or suspicious

LE PATIENT Vol. 9, nº 1 1716 LE PATIENT Vol. 9, nº 1

What is the location of the neoplasia?

The degree of metabolism of a tumor must be putin relationship with the basal metabolism of theorgan in which the tumor is sought (Figures 2 and3). In some cases, this can cause interpretationproblems and can limit the sensitivity of the exami-nation. The bladder comes in at the first place ofhypermetabolic organs due to the physiological uri-nary excretion. Fortunately, it is easy to significantlydecrease the physiological activity in urinary bladderby diluting its activity through the i.v. administrationof furosemide. This protocol allows therefore toimage high grade bladder cancer and to make theassessment of its extension (Figure 10). In contrast,since this is not a procedure carried out on allpatients, it is important to specify in the request forexamination if there is a suspicion of bladder neo-plasia, lesion to the outer wall (implant of a gyne-cological neoplasia) or at the edge of the bladder(metastatic lymph node). The brain comes in secondplace of hypermetabolic organs. Unlike the bladder,there is no easy method to decrease brain activityother than by sedation. It is therefore difficult tolocate brain metastases in this physiologically veryactive organ. MRI remains the imaging of choice inthe assessment of neoplastic cerebral lesions, butPET is the imaging of choice for monitoring postradiotherapy response.

What is the size of the lesion under evaluation?

The sensitivity and resolution of PET equipment isincreasing from year to year. In the optimal condi-tions, the technology currently available can detectlesions in the vicinity of 4.5 mm. Unfortunately,these perfect conditions are almost impossible toobtain in the human body, and a reasonable esti-mate of the camera resolution would be at about 6mm. If the anomaly to be imaged is sought in amobile organ, the sensitivity decreases as a functionof the amplitude of the movement. It is thereforedifficult to identify a nodule of 6 mm located at thebase of the lung or an infra-centimeter hepaticmetastasis juxtaposed to the diaphragmatic dome.To overcome this limit, imaging techniques synchro-nized with the respiratory rate are now available(respiratory gating).

What is the histological type of the initial tumorand its grade in a context of staging, restagingor when evaluating treatment response?

The higher or more undifferentiated histological thegrade is, the more it will accumulate 18F-FDG. Becauseof their low glucose metabolism, some histologicaltypes do not uptake any or will accumulate very littleof 18F-FDG so that the role of PET with FDG is limitedfor these types of tumors: well differentiated prostatecancer, some hypernephroma, small lymphocytic lym-phoma (chronic lymphoid leukemia), marginal zonelymphoma, lymphoplasmocytary lymphoma(Waldenstrom), leukemia, well differentiated hepato-cellular carcinoma, minimally invasive lung carcinoma

Figure 6 :PET FDG is not only useful in oncology. It can be used for the diagnosis and monitoring of giant cell arteritis, the search for infectious foyers (ex: infection of orthopaedic materials), the diagnosis of myositis/dermatomyositis and even in the assessment of inflammatory intestinal diseases.

Figure 7 :Active chronic inflammatory granulomatosis conditions, like sarcoidosis, can resemble a lymphoma (center), or even a plurimetastatic disease (right).Some criteria, including the symmetric hilum distribution, the disproportionbetween the size of lymph nodes and their activity, the presence of lymphnodes and splenic calcifications, are elements in favor of a granulomatous disease. In cases where presentation is more atypical (image on the right),only a biopsy can differentiate between the two entities.

Figure 8 :Evaluation of an undetermined lung nodule. Left Images (CT and PET): Lungnodule to the lingula presenting no significant metabolic activity, compatiblewith a benign/inflammatory nodule (blue arrows). Center Images (CT andPET): Lung Nodule near the left hilum presenting very significant metabolicactivity that is compatible with primary pulmonary malignancy (red arrows).Right Image (PET alone): Plurimetastatic disease (bone, lymph nodes, adrenalglands) from the left lung.

Table 2:

Brain : • Relapse versus radionecrosis of high-grade gliomas post-

radiotherapy• Primary brain tumor versus metastasis: primary site search

Head and neck :• Search for a primary site explaining metastatic cervical adenopathy • Initial staging in suspected advanced stage • Residual disease assessment post-treatment

Thyroid :• Thyroid cancer when thyroglobulin level is elevated and radioiodine

scan is negative• Staging and restaging of poorly differentiated thyroid cancer,

Hurthle carcinomas, or medullary thyroid carcinomas

Lungs :• Classification of an undetermined lung nodule • Pre-operative staging assessment • Radiotherapy planning in case of significant lung atelectasis• Relapse versus scar tissue formation post-surgery or post-radiation • Lower sensitivity for the bronchiolar-alveolar adenocarcinomas

Breast : • Initial staging and follow-up of locally advanced or metastatic

cancer when conventional imaging studies are equivocal or suspicious

• More accurate in triple negative cancers or HER-2 overexpression• Less sensitive if lobular or well differentiated

(hormonosensitive breast cancer)

Oesophagus : • Initial staging to assess respectability • Restaging after an induction chemotherapy and/or radiation• Response to treatment• Radiotherapy planning

Stomach :• Useless in the detection of a primary • Only useful in metastatic assessment

Liver :• Differentiate between benign or malignant lesions when

conventional studies are equivocal or suspicious• Search for liver metastases• Cholangiocarcinoma (other than tubular or mucinous)• Less useful for the well differentiated hepatocellular carcinoma

Pancreas : • Pre-operative metastatic assessment• Less useful in the characterization of a mass

Colorectal :• Local Recurrence versus scar tissue• Unexplained markers elevation (CEA) in post-therapy context• Pre-surgical evaluation of a single liver lesion• Pre-operative adenopathy assessment and search for metastases • Treatment response • Less sensitive in the presence of significant mucinous component

Melanoma :• Search for metastases (Breslow > 1.5 mm), Stages II and III• Restaging in patients with recurrent disease following therapy• Less useful in Stage I, because the metastatic risk is < 5 %

• Hodgkin and non-Hodgkin lymphoma :• Routine pre-treatment staging • Measure treatment response, chemotherapy and radiotherapy• Evaluation of relapse • Restaging before bone marrow graft• Guide biopsy to the most accessible site

Gynaecologic (cervix) :• Preoperative staging assessment • Detection of residual disease after treatment• Restaging at relapse• Could be of interest for radiotherapy planning

Testicular :• Search for metastases• Chemotherapy / Radiotherapy response evaluation• Teratoma content may cause false positive and false negative

studies• Residual mass assessment/surveillance

Bladder (with iv Lasix, voided bladder) :• Preoperative staging• Search for metastases in the context of relapse• Treatment response evaluation

Prostate :• Should not be used if well differentiated histology and Gleason < 8• Staging if histologically undifferentiated

Sarcoma :• More sensitive in high grade sarcomas• Low grade tumors are frequently false negative

(bronchiolo-alveolar), any tumors with high mucincomponent, low grade neuroendocrine tumor, lowgrade sarcomas (particularly liposarcoma), teratoma,and some well differentiated breast cancer (particu-larly the lobular carcinoma).

How much time should we wait between a PETstudy and the last surgery, radiotherapy orchemotherapy?

Especially for the evaluation of a local recurrence orthat of a treatment response, it is recommended to

wait four weeks between the PET study and surgeryor chemotherapy, or to wait three months after thelast radiation treatment, since the local residualinflammation could cause false positive results. Ifperformed too soon post-treatment, the evaluationmay be associated, depending on the case, to a high-er rate of false positives or false negatives. It is alsoimportant to mention that if the patient is under hor-monal therapy, this medication can also affect PETresults, same as chemotherapy.

18 LE PATIENT Vol. 9, nº 1 LE PATIENT Vol. 9, nº 1 19

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patient care.

Is there an infection nearthe site under evaluation?Is the patient known for anon-neoplastic disease thatnaturally uptakes 18F-FDG?

FDG PET does not provide away to differentiate between aneoplastic lesion and an activeinfectious or inflammatoryprocess (Figure 6), since thetwo latter will avidly capturethe 18F-FDG. It is therefore dif-

ficult, for example, to differentiate active tuberculosisfoyer from a primary pulmonary malignancy or anabdominal abscess of a colonic neoplasia from a lym-phoma. Some benign pathologies, like sarcoidosis,active Wegener, tuberculosis, uterine fibroid, thyroidi-tis, stomach ulcers, acute or chronic cholecystitis andmany others may capture FDG. Without biopsy of thelymph node, it is often difficult to differentiate by PETa sarcoidosis from a metastasis or a lymphoma (Figure7), a uterine fibroid tumor from a sarcoma or yet, thehistiocytosis from a multifocal bone metastasis.

In other words, FDG may accumulate in places withactive inflammation, be it acute, chronic, infectiousor granulomatous. The distribution of the radiotracerand the appearance of lesions can sometimes allowthe nuclear medicine specialist to distinguishbetween an infection, an inflammatory process or aneoplastic lesion, but it is important to rememberthat these conditions represent the most frequentcause of false-positive results.

FDG PET is now the oncology standard for severaltypes of cancers. This very powerful diagnostic tool isonly in its early stages in Canada and will be calledupon even more in the coming years. Even if FDG isan excellent radiotracer for tumors and metastaseslocalization, some cancers cannot be easily assessedwith this radiotracer. Consequently, there is a need fornew clinical tracers to increase the diagnostic accura-cy of PET for cancers where FDG is less efficient.Sodium fluoride is one of the new tracers in clinicwhich allow earlier detection of the bone metastases(Figure 11). 18F-MFES, an oestrogen derivative underclinical trial in BC and Quebec, is one of the mostpromising tracers for the detection and staging ofhormonosensitive breast cancer (Figure 12).

Since there are multiple factors to consider in a FDGPET study, it is crucial to provide maximal clinical infor-mation to the nuclear medicine specialist who will beinterpreting the imaging results (pathology reports,summary of surgical procedures, radiology results,blood biochemistry) in order to give a more preciseanswer to the clinical question. And, for more com-plex cases, a discussion with the nuclear medicine spe-cialist may be relevant before prescribing the exam.

Figure 9 : FDG PET performed while taking metformin.Metformin modulates a highly intense FDG

accumulation in the bowel (blue arrows) whichmakes it impossible to detect bowel lesions.

Metformin should be stopped at least two daysbefore FDG PET.

Figure 10 : In the physiologically hypermetabolic organs,some maneuvers may be attempted in order todecrease the basal metabolism and to allow visualization of the tumor. Bladder cancer is thetypical example of how the use of a diuretic helps the bladder to drain quickly so that thetumor can be easily set apart (black arrows).


Figure 11 : The future of the PET lays within the development of new radiotracers enablingsensitivity increase of already existing exams and/or newer indications. The development of sodium fluoride PET (NaF PET) as a replacement for the conventional bone scan is an example. This study is carried out 30 to 45 minutesafter the injection of the radiotracer and the acquisition of the images only lasts for 35 minutes (compared to a waiting time of 4 hours and 40 minutes imaging, on average, for a regular bone scan). With NaF PET, which is more sensitive andfaster, it is possible to locate metastases as small as 5 mm.

Figure 12 :PET performed with18F-MFES, an oestro-

gen derivative highlysensitive to detecthormonosensitivebreast cancer and

metastasis. Clinicaltrials, funded by the

Canadian BreastCancer Foundation,

are underway inQuebec and in theinitial phase in BC.Red arrow: Primarybreast cancer. Blue

arrow: axillary metastasis. Purple arrow: internal mammarymetastatic lymph node. Black arrows: Bone metastasis.

Nuclear Medicine plays a vital role in the diag-nosis of the patient with heart disease on adaily basis in hospitals and clinics across this

country. In addition to aiding diagnosis, it frequent-ly guides or directs therapy as well as monitors thesuccess of those therapies in cardiac patients. Wewill look at its role in routine clinical practice andhow it is best utilized given some common clinicalsettings.

Let’s familiarize ourselves with the most commontechniques used in Cardiac Nuclear Medicine today.

MYOCARDIAL PERFUSION IMAGING

By far, the most frequent tool used in CardiacNuclear Medicine departments is the MyocardialPerfusion Imaging study (MPI). This technique waspreviously more commonly referred to as a stressThallium study. It has been re-named because the

radiotracer used previously, Thallium-201, has beenreplaced for the most part by Technetium-99m-MIBI(MethoxyIsoButylIsonitrile) or Tc99m-Myoview(Tetrofosmin). These latter two agents allow betterimages of the heart using the current Single PhotonEmission Computed Tomography or SPECT camerasin use today.

MPI involves injecting these tracers intravenouslywhich localize within the heart muscle in direct rela-tion to a patient’s cardiac blood supply. The tracerdistribution reflects this blood supply at the time ofinjection providing a “snapshot” of what hasoccurred up to three hours earlier when imagedunder the camera later. Thus, a patient who isstressed on a treadmill or who is injected while hav-ing a spontaneous episode of chest pain can beimaged later when stable and the images can becompared to a study done while the patient is at restor pain-free.

Kevin P. Tracey

MD, FRCPC, ABNM

Medical Director- NuclearMedicine

Hotel-Dieu Grace Hospital1030 Ouellette AvenueWindsor, ON N9A 1E1


NUCLEAR MEDICINE IN THE DIAGNOSIS OF HEART DISEASE

Also, in addition to looking at heart perfusion, wecan look at wall motion and wall thickening withthese agents using a technique called “gatedSPECT.” From this, we can estimate the heart’sEjection Fraction or EF, which is a valuable measure-ment tool of the heart’s pumping ability.

Stress MPI is performed in two steps. The first stepinvolves an injection of Tc99m-MIBI or Myoview atrest. Imaging under the camera is typically per-formed an hour later. Later the same day or on aseparate day, the patient is exercised on a treadmillor, in patients unable to walk on a treadmill, given adrug that gives the same information as exercise.

Dipyridamole (or in the USA Adenosine) is used asthe stressing drug in most patients who cannot ade-quately exercise, but also in patients who have a LeftBundle Branch block on ECG or patients who can-not or have not stopped their beta-blocker medica-tion. It is contraindicated in uncontrolled asthmatics.Dobutamine is an alternativestressing drug for thosepatients.

At peak stress they are injectedwith the Tc99m-MIBI orMyoview and imaging repeat-ed. The computer generatedimages of the blood supply tothe heart are compared, slice byslice (Figure 1). These areinspected visually by thenuclear medicine physician, butare also compared to a sex-matched normal database.Perfusion defects present atrest generally indicate previousmyocardial infarction (althoughartifacts and chronicallyischemic tissue can also appearthis way) (Figure2).

Reversible defects, that is,defects occurring during theexercise or stress study only,which show normal blood sup-ply at rest, represent ischemicareas of heart tissue which areat risk for a myocardial infarc-tion or heart attack (Figure 3).

The investigation of patients atrisk for ischemic heart diseaserequires assessing the pre-testlikelihood of disease in a partic-ular patient. This is because MPIis best used for patients at anintermediate risk of having thedisease.

MPI is generally a second tierstudy done in patients who

have undergone a previous treadmill study in whoma diagnosis of ischemic heart disease cannot bemade or in whom the volume of at risk myocardiumneeds to be determined. It is, however, also of greatuse in patients with resting ECG changes in whom astandard treadmill study will be non-diagnostic. Asmentioned, pharmacologic stress MPI studies are afirst tier study in patients who are unable to exer-cise, in patients unable to achieve a heart rate of85% of their age-predicted maximum heart rate,but also in LBBB patients, because of a specific false-positive finding that occurs when these patientsundergo a treadmill MPI.

Also, Persantine (or dipyridamole) MPI is particularlyuseful in the early days following a heart attack,when it can be safely used to study a patient as analternative to exercise.

Increasingly, Stress MPI nuclear studies are beingused as an initial investigation in women at interme-


diate risk for heart disease and diabetic patients, aswe recognize the difficulty in diagnosing cardiac dis-ease in these patients. Often, heart disease is silentand the standard treadmill study alone misses dis-ease in these and other higher risk patient popula-tions.

Stress MPI is used to direct which vessel is the likely“culprit” vessel in patients with two or more knowndiseased coronary arteries. Furthermore, once apatient has been treated either with bypass surgery,angioplasty or stent or with medical therapy, MPI isused to monitor response to therapy.

Pre-operative risk assessment of patients at risk for acardiac “event” during or following surgery, partic-ularly vascular surgery, is another common and vitalrole for this technique. The categorization ofpatients into low versus intermediate versus highrisk frequently allows for identifying and treating apatient’s heart disease before they have what mayotherwise be a fatal surgical complication.

In some centers, injection of patients who present tothe ER with chest pain with MIBI or Myoview can bea valuable tool when the ECG and enzyme markersare non-diagnostic. The presence of a normal exam-ination can allow for early discharge and a low-riskcategorization.

By far the most common use of this technique is inchest pain assessment. More and more in this coun-try the MPI allows appropriate risk stratification andserves frequently as a gate-keeper to diagnostic car-

diac catheterization. This non-invasive tool allowsthe most strategic and cost-effective use of thismore limited resource.

Utilizing the technology of CT scanning, combinedwith Nuclear Medicine SPECT gamma cameras,SPECT-CT systems are now in place in most majorcenters. Using a low-dose CT of the heart done inconjunction with the gated SPECT MPI studyreduces the number of artifacts in women andobese patients secondary to breast tissue and softtissue “attenuation” artifacts respectively. Thenormal loss of information in these patient’s stud-ies is corrected by data from the CT study. Theradiation dose received by the patient from thesestudies is low and still well within the diagnosticrange.

Ancillary information such as coronary artery calcifi-cation and even unsuspected lung and breast can-cers have frequently been incidental discoveries dur-ing these procedures.

MULTI-GATED CARDIAC STUDY OR MUGA

The Multi-Gated cardiac study or MUGA is theother most common tool used daily in NuclearMedicine departments. It is sometimes referred toas an Equilibrium RadioNuclide Angiogram (ERNAor RNA) or Gated Blood Pool Study. This studyinvolves labelling a small sample of the patient’s redblood cells with the radioisotope Technetium(Tc99m) and then re-injecting them intravenously.The labelled red cells remain for the most part inthe blood pool and dynamic images of the heart areobtainable.

The “gating” relates to the recording of the data rel-ative to a particular segment of the cardiac cyclewhen timed to the patients ECG complexes. A com-posite moving image of the heart is built up over aperiod of anywhere from two to ten minutes. Theimages can be acquired with the SPECT techniqueas well, resulting in both 2D and 3D images. Theyare then visually assessed for wall motion abnormal-ities. While typically done as a resting study, StressMUGA examinations can also be performed.

Echocardiography is used more commonly to assessthe heart non-invasively because of its ability toassess both wall motion and structure as well asvalve assessment without exposing the patient toradiation. The MUGA study is still important today,however, for its ability to more accurately quantitatethe Left Ventricular Ejection Fraction (LVEF), animportant measure of cardiac function.

MUGA studies utilize a more accurate and repro-ducible “count based” method for determination ofthe LVEF rather than a geometric formula. Its valueas a monitoring tool such as in patients at risk forchemotherapy-induced cardiotoxicity or for optimal


Pub SEGAMI

selection of patients for techniques such asImplantable Cardiac Defibrillators makes it still inwide use today.

Stress MUGA studies are also still performed by labsutilizing the response of a patient’s LVEF while exer-cising as a tool to help decide on the timing of valvereplacement.

First pass cardiac techniques can be used in conjunc-tion with the MUGA study to assess for intracardiacshunts and to obtain quantitative information aboutthe Right Ventricle. This technique of obtaining veryrapid images and radioactivity counts as the injectedtracer passes through the heart on its first pass iso-lates the different chambers and allows for RVEFdetermination as well.

MYOCARDIAL VIABILITY STUDIES

In patients where large rest defects are seen on aMPI study and heart failure is present, the possibili-ty exists that the defects represent areas of chroni-cally ischemic and hibernating myocardium, ratherthan dead or infarcted tissue. This is importantbecause by bypassing these patients, they canregain cardiac function. PET or Positron Emission

Tomography is the most accurate tool for assessingfor hibernating myocardium. Its availability remainslimited, however, and in many centers Thallium-201viability imaging can make the diagnosis albeit withreduced sensitivity.

Patients are injected at rest and a SPECT cardiacstudy is performed after 30 minutes. A repeat studyis then performed at four hours after the initialinjection. The studies are combined and computeranalyzed. Areas of thallium redistribution representviable but hibernating myocardium. A negativestudy does not exclude potentially salvageable tis-sue, however, and the patient may still benefit fromPET imaging.

SUMMARY AND FUTURE DIRECTIONS

We have discussed the most common CardiacNuclear Medicine procedures used in clinical prac-tice today. Less frequently utilized studies such asimaging of Cardiac Denervation using MIBG(MetaIodoBenzylGuanidine), imaging of Apoptosis,Atherosclerotic imaging and other exciting andevolving Molecular Imaging techniques promise a“new and clear” future for Cardiac NuclearMedicine.


A Unique Platform: The Canadian Experience Historically, nuclear medicine has benefited from excellent software but, rarely on a single platform. One computer is generally used to display a certain type of exam, another to archive the data and, another is used for specific or dedicated applications.

experienceHERMES Medical Solutions is proud to take part in this year’s special nuclear medicine edition alongside its fellow industry partners and family of 28,000 users.

With 39 years of experience as a medical imaging software leader, HERMES is dedicated to meet and exceed the clinical, developmental, educational and research needs of its users. Pro-viding state-of-the-art software, HERMES offers innovative and cost effective healthcare solu-tions while maintaining the high-est medical imaging quality stan-dards, playing a key role in the patient continuum of care.

The HERMES SUV-SPECT™ revolutionizes quantitative imaging by exploiting the use of SPECT’s full potential in regions where a large portion of the population still does not have access to PET and/or associated

reimbursements. HERMES SUV-SPECT™ software algorithms enable a conversion of the recorded counts per voxel into activity per unit volume with SUV calculations, providing essential and accurate quantitative results.

HERMES VNM™ includes HERMES VNA (Vendor-Neutral Archive) combined with the power of a complete clinical medical imaging platform, tailor-made for multi-vendor sites/multi-facilities integration. HERMES provides

cost effective solutions worldwide from enterprise-wide architecture & infrastructure to storage, reading, analysis and processing services on its systems or via HERMES cloud, TeleHERMES™.

René RebeaudManaging Director

François HébertSales Director

Benoit GalarneauResearch and Development Director

Caroline RochetteSenior Project Manager

Accuracy with

Previously used for teaching purposes or display modelling, 3D applications now enable automatic lesions detection or the ability to establish more accurate diagnostics in comparison with still largely used 2D tools.

Quantification

Improved prognosticHERMES is extremely proud to

participate in high-level research

to support healthcare profes-

sionals in the detection and

treatment follow-up of diseases

such as epilepsy, brain tumors,

schizophrenia, Parkinson’s and

most recently Alzheimer’s. New

amyloid tracers, which are mak-

ing their debut on the market,

will facilitate HERMES efforts

in assisting physicians world-

wide in university facilities as

well as in community hospitals,

by providing them with normal

templates for a precise and reli-

illness state. HERMES BRASS™

(Brain Registration & Analysis

Software Suite) has appeared

publications and presentations

around the world and has been

validated with over 2 million

patients.

team work

HERMES employs a solid team

of 21 members, dedicated to

quantitative molecular imaging

in Canada.

wordlwide

in Sweden, Canada, the United

Kingdom and the United States.

These amazing results can be obtained with the help of advanced segmentation methods especially useful with quantitative pulmonary studies. The Hybrid Viewer™ 3D module proceeds with an automatic co-registration of the SPECT-CT (and sepa-rate diagnostic CT if needed), an automatic L/R Lung and airways segmentation, a quick

-tion quality control, a lobar ventilation and

report generation. Knowing that accurate results can drastically change the optimal

surgical approach, comparative studies have been conducted between current 2D tech-niques (planar anterior image or real ante-rior reprojection divided in 6 segments) and 3D segmentation techniques. Preliminary results have shown differences ranging be-tween -10% to +48% in the assessment of accurate volume calculation in ml.

Similar tools for automatic hepatic and kid-ney segmentation are now available and will help promoting for a closer collaboration between quantitative imaging and surgical departments.

The lack of integration and the non-unifor-mity of components, continues to cause se-

working in imaging departments.

With crucial input from Canadian custom-ers and nuclear medicine pioneers, the Montreal-based HERMES R & D team has developed Hybrid Viewer PDR™: A unique and user-friendly software for Processing, Display and Reporting (PDR). This all-in-one tool allows the display of all medical imaging modalities (including angiography and ultra-sound), image fusion (SPECT-PET-CT-MR) including analysis of this data, processing of conventional nuclear medicine and, the abil-ity to generate medical reports. This tech-nology is used across Canada and present in about 80% of NM Departments in the Province of Quebec.

The raw and processed data is then stored in a metadata VNA in DICOM, native for-mat, MS-Word™, MS-Excel™, .wav audio

existing equipment in today’s departments under a single master worklist.

distinguishing from other imaging modali-ties. The arrival of Positron Emission To-mography (PET and its SUV scale) certainly

essence of nuclear medicine still remains the Single Photon Emission Computed Tomog-raphy (SPECT) environment for a vast ma-jority of Canadian medical centers. The new breed of cameras coupled with CT compo-nents and optimized with advanced recon-struction tools started paving the way for the day when a-SUV scale, similar to the one used in PET, would help us quantify images obtained from SPECT-CT scanners. Despite the increasing availability of PET, the num-

-nique is still suboptimal. Absolute SPECT-

opens the door to a plethora of possibilities with dozens of proven tracers already in use.

HERMES SUV-SPECT™ HERMES VNM™

RAYMOND TAILLEFERMD, FRCP, ABNM

Chief of department ofnuclear medicine of

Hôpital du Haut-Richelieu, Professor of nuclear medi-cine, department of radiol-

ogy, radio-oncology andnuclear medicine,

Université de Montréal.

acquisition. This can be obtained approximately 15-30 minutes after the injection of 99mTc-pertechne-tate, either with a regular planar gamma camera(usually 2 or 3 different views, thoracic anterior pro-jection, left lateral and the best septal left anterioroblique view) or in tomoscintigraphic mode (whichhas been more recently introduced in clinical prac-tice), using 32 or 64 views around the thorax, givinga better evaluation of the right ventricle and a bettercontrast resolution between the various cardiacchambers.

Dynamic images must be obtained in order to evalu-ate the contractility and to determine the ejectionfraction of the left and right ventricles. These dynam-ic images can be obtained by the synchronization ofthe images with the patient’s ECG. Therefore, eachimage from radionuclide ventriculography is synchro-nized to the ECG. Patient’s cardiac cycle is dividedinto 16, 32 or 64 “frames” or image series. Theseframes are usually obtained over a period of approx-imately 10 minutes per planar projection and then, asingle representative cardiac cycle is reproduced fromthese multiples cardiac cycles. The final image is thenshown in a continuous loop and does not representonly one cardiac cycle but rather a significant num-ber of cardiac cycles (approximately 700 cardiaccycles which are added together); this is called therepresentative cycle. The major advantage of thisprocedure is related to the fact that all parametersare not obtained from a single cycle but from a largenumber of cycles, which is much more representativeof the patient’s physiology, and allow for rejection ofirregular cardiac cycles during data acquisition.

DATA ANALYSIS

The major clinical advantage of equilibrium radionu-clide ventriculography relies in its capacity to deter-mine cardiac volumes, no matter the size or shape ofthe cardiac chambers. In contrast to geometric meth-ods (radiologic angiology, echocardiography...),radionuclide ventriculography uses a volumetricmethod which is more precise and effective to deter-mine the ejection fraction of the left ventricle (LVEF)or the right ventricle, and also ventricular volumes.This degree of precision is related to its volumetricmethod of calculation and the fact that the study isobtained on a large number of cardiac cycles.

The calculation of the left ventricle volume and LVEFis based on the count density detected by thegamma camera. The number of counts originatingfrom the left ventricle is directly proportional to thenumber of radiolabeled red blood cells within theventricle. A region of interest is traced on the com-puter over the left ventricle at end-diastole.Following this step, a specific software will automat-ically detect the contours of the ventricle for eachframe of the cardiac cycle. The LVEF is thus preciselycalculated by comparing the number of left ventriclecounts at end-diastole to the number of counts atend-systole from the time-activity curve recorded bythe computer (figure 2). In planar acquisition, it is

more difficult to clearly delineate the right ventriclebecause of superimposition of other cardiac struc-tures. Tomoscintigraphic acquisition is thus preferredbecause of its better accuracy to determine the ejec-tion fraction of the right ventricle (figure 3).Tomoscintigraphic acquisition allows for a betterdelineation of the various cardiac chambers and their


Clinical cardiac nuclear medicine began approx-imately 50 years ago with the introduction ofradionuclide angiography. Functional cardiac

evaluation with radionuclides started in 1962 withdirect administration of a radionuclide into the leftventricle during cardiac catheterization, withoutobtaining external images. It is only in 1971 that thepredecessor of radionuclide ventriculography wasobtained with a noninvasive radiotracers intravenousinjection in the arm, with images of the heart andsynchronization of these images with the patient’selectrocardiogram (ECG) signal. There are two majortypes of radionuclide ventriculography. The first-pass studies (or angiography), that is the dynamicstudy of the first-pass of the radionuclide into thecardiac cavities (mainly the ventricles) following itsintravenous injection into the veins of the arm andequilibrium ventriculography, which is the studyof the ventricle contractions over a representativenumber of cardiac cycles (therefore, the term “equi-librium” in comparison to the first-pass study wherethe acquisition is performed on a single cardiac cycleand not on a large number of cycles). Radionuclideventriculography can be performed either at rest orafter a stress test, either on a treadmill, on a bicycle,or following administration of pharmaceuticalagents. Equilibrium radionuclide ventriculography, atrest, is by far the most common type of ventriculog-raphy used in clinical practice, and our discussion willbe limited to this type of ventriculography.

RADIOTRACER

Various types of radiotracers have been used forradionuclide ventriculography, especially for the first-pass studies. The ideal radiotracer must remain in theintravascular blood pool compartment for a suffi-cient time to allow for image acquisition and a back-ground activity as low as possible in adjacent organsto the heart. The most frequently used technique toachieve these goals is the labeling of patient’s redblood cells with 99mTc-pertechnetate. The red bloodcells labeling is a simple and easy procedure. Thereare various methods to label the red blood cells butthe basic principle remains the same. The labeling ismediated by a reducing agent, stannous pyrophos-phate, which binds both the surface of the red bloodcells and the sodium 99mTc-perctechnetate, which isthe radiotracer detected by the external gammacameras. In an initial step, stannous pyrophosphateis injected intravenously, followed by the intravenousadministration of 99mTc-pertechnetate (figure 1).The labeling efficiency of the red blood cells is morethan 90% and is stable for several hours, allowingfor longer acquisition time, especially when the car-diac rhythm of the patient is irregular.

DATA ACQUISITION

Following the patient’s red blood cells labeling, thesecond step of the process is the scintigraphic data

CLINICAL APPLICATIONS OF RADIONUCLIDE VENTRICULOGRAPHY


Figure 1. Example of a first-pass study of a radioactive bolus containing redblood cells radiolabeled to 99mTc-pertechnetate, through the various cardiacchambers from a simple and noninvasive antecubital vein.

Figure 2. Regions of interest in end-diastole obtained from a planar study toprecisely determine the LVEF (in this case 56%, from a time-activity curve derivedfrom a representative cardiac cycle). Many other parameters can be obtained aswell from the time-activity curve such as filling rates, ejection rates etc...

superimposition, the result being a better contourevaluation of the right ventricle and its activity duringthe cardiac cycle.

The high resolution of the computer generated time-activity curve allows for calculation of LVEF and RVEF,as well as other parameters such as ventricular vol-umes, peak filling rate, ejection rate… just to name afew. Furthermore, planar and mostly tomoscinti-graphic studies provide a very good evaluation of theglobal and regional contractility status of both rightand left ventricles

CLINICAL APPLICATIONS

Radionuclide ventriculography has been used in theevaluation of almost all types of cardiac diseases. Thisprocedure does not have the high anatomic resolu-tion of echocardiography or magnetic resonance nec-essary to evaluate the ventricular mass or anatomicdetails of the cardiac valves. However, radionuclideventriculography is recognized as the gold standardto precisely evaluate the LVEF. The LVEF remains, todate, one of the best and most effective predictors ofa patient’s outcome with coronary artery disease, car-diac valvular disease or cardiomyopathies.

Table 1 summarizes the major clinical indications ofradionuclide ventriculography as described in theguidelines from the American College of Cardiology,American Heart Association and American Society ofNuclear Cardiology. These indications are not limitedbut are established from studies demonstrating theclinical usefulness of both planar and tomoscinti-graphic radionuclide ventriculography in the determi-nation of LVEF and the study of global and regionalcontractility of both right and left ventricles.

The great accuracy of radionuclide ventriculographyin the evaluation of LVEF makes it a very importantdiagnostic and follow-up tool in patients treated withcardiotoxic chemotherapy. The determination of theLVEF is important since an early decrease of it allowsfor an early diagnosis of cardiotoxicity and a subse-quent change in the treatment to avoid irreversiblecardiac damage. Radionuclide ventriculography is thebest and most accurate method to perform a follow-up of these patients. Radionuclide ventriculography isthe gold standard used in clinical research to followcardiotoxicity.

The various parameters obtained from radionuclideventriculography (especially LVEF, RVEF, and globaland regional contractility) can be noninvasively andeasily obtained in the diagnosis, prognosis and fol-low-up of various cardiac diseases.

CONCLUSIONS

Planar radionuclide ventriculography and morerecently tomoscintigraphic ventriculography is a sim-ple, reliable and accurate procedure allowing for pre-cise determination of the ejection fraction of boththe right and the left ventricles and global andregional cardiac contraction as well. This is an impor-tant and complementary diagnostic tool to echocar-diography and magnetic resonance.


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Figures 3a, b. Tomoscintigraphic radionuclide ventriculography allow-ing for a clear delineation of the right from the left ventricle and thus hav-ing a more accurate determination of the LVEF and RVEF.


DaTSCAN (I123 ioflupane) is a radiolabelled tracerwhich is used for differentiation of Parkinson’sdisease from Essential tremor and also in differ-

entiation of Dementia with Lewy bodies (DLB) fromAlzheimer’s dementia.

Parkinson’s disease (PD) is one of the most commonchronic neurological disorders affecting over 127,000people in the UK, a million in the USA and, 100,000in Canada. Its prevalence is set to rise by around 25%by the year 2020 using available population trends.The condition is caused by degeneration and loss ofneurons in substantia nigra in the brain. These cellssend tentacle (axons) to another part of the braincalled striatum (compromised of Caudate andPutamen, figure 1), where dopamine (a neurotrans-mitter) is produced and stored. Dopamine is a sig-nalling chemical in the brain which regulates complexfunctions including voluntary and involuntary move-ments. The brain has a huge compensatory capacityso the symptoms of Parkinson’s disease are notdetected until approximately 60% of these neuronsand their associated axons are lost. Patients may then

present with one or more of the clinical features oftremor, slowness of movement and stiffness (rigidity).The condition progresses over a period of years,resulting in progressive disabilities including freezing,difficulty in walking, pain, eye problems, communica-tion problems, expressionless face and depression.The diagnosis of Parkinson’s disease can be difficult asthe symptoms may initially be subtle and also occur inother neurological conditions, such as essentialtremor (a common and benign condition).Misdiagnosis is not uncommon even by clinicianswho specialize in movement disorders. Correct diag-nosis of this condition is important for the patient,the carers and for correct treatment of symptoms.

Dementia is another global challenge with increasingrecognition of its devastating effect on people’s livesand that of their carers. Over 800,000 people in theUK, 5.2 million in the USA and 700, 000 in Canadaare diagnosed with dementia, and this number isincreasing with growth in the elderly population.Alzheimer’s dementia is the most common form ofdementia (50-70%) and DLB accounts for 10-15% of

dementias. DLB is thought to be underdiagnosed. It isimportant to get an accurate diagnosis as there aredrugs which can benefit and also drugs to be avoid-ed in patients with DLB. DaTSCAN can be used fordistinguishing DLB from other forms of dementia.

DaTSCAN (also known as ioflupane & FP-CIT) wasfirst licensed for clinical use in Europe in July 2000,and was approved by the FDA (USA) in August 2009.It is currently licensed and used in 34 countries andhas so far been used in more than 300,000 patientsworldwide. DaTSCAN binds to dopamine trans-porters in dopaminergic nerve terminals in the striata(caudate and putamen). As mentioned earlier, there issubstantial loss of dopaminergic nerve terminals(>60%) in both Parkinson’s disease and DLB beforethe clinical signs and symptoms are seen. DaTSCANimaging can detect this loss of neurons and nerve ter-minals with minimal symptoms, enabling earlier andmore accurate diagnosis of these conditions. There isoften a preferential loss of these nerve terminals inthe putamen, changing the normal comma shapedappearance of the striata (figure 2) to that of a dotappearance in Parkinson’s and DLB patients (figure 3).Quantification can help to further confirm this in ear-lier and in more difficult cases.

DaTSCAN is a nuclear medicine investigation andcomes in a ready-to-inject solution containing 185MBq (5 mCi) of I123-ioflupane. This is injected intra-

venously. No special preparations are necessary andthere is no need to stop most of the anti-Parkinson’s/Dementia medication. The patient under-goes SPECT imaging 3 to 6 hours later using a stan-dard SPECT gamma camera available in most nuclearmedicine departments. The images take around 30minutes to produce, during which time the patients’head is kept still. Images are then appropriatelyprocessed using standard software and reported by anuclear medicine physician. The accuracy of this testis shown to be more than 95% for both indications.

In conclusion, DaTSCAN imaging is a safe and effec-tive new addition to the nuclear medicine portfolio,accurately diagnosing patients with Parkinson’s dis-ease and DLB and confidently excluding the diseasein those patients who actually do not have the dis-ease, improving the management of patients withdementia and with movement disorders.

DATSCAN FOR DIAGNOSINGPARKINSON’S DISEASE AND DEMENTIA WITH LEWY BODIES (DLB)

Dr Alp NotghiMD, MSc, FRCPE,

FRCPLConsultant Physician in

Nuclear MedicineDepartment of physicsand Nuclear Medicine

Sandwell & WestBirmingham Hospitals

NHS TRUST City Hospital

Birmingham England

Dr Manish PanditMBBS, FRCS, FRCSENT,

MSc, DipCBNCPresident of British

Nuclear MedicineSociety

Figure 1:MRI section of brain showing caudate andputamen (striata). The dopaminergic nerve termi-nals in these structures are affected in Parkinson’sDisease and in DLB. There is DaTSCAN uptake inthese structures in a healthy individual. In PD andDLB, DaTSCAN uptake is progressively reduced inthese structures.

Figure 2:DaTSCAN normaluptake in striata showing the typicalcomma shaped appearance on bothsides. The “head” of the comma is the caudate and tail of thecomma is the putamenuptake in the striata.

Figure 3:DaTSCAN uptake in apatient with idiopathicParkinson’s disease.There is preferential lossof uptake in putamen ina patient with idiopathicParkinson’s disease, producing the typical dot appearance of thestriatum (with only caudate uptake remain-ing). Furthermore, notethe increased relativebackground activity inthe image, also indicat-ing that there is loss ofuptake in the remainingcaudate.


Philip F. Cohen MDFRCP(C)

Division Head, NuclearMedicine

Lions Gate HospitalAssociate Professor

RadiologyUniversity of British

Columbia

Osteomyelitis is a diagnostic problem becausesignificant bone destruction must occurbefore it can be seen on regular x-rays or CT

scan. MRI is a sensitive test, but is not routinely avail-able in most Canadian hospitals. MRI, also, is notparticularly good at whole-body imaging where aninfection other than osteomyelitis is being consid-ered.

Nuclear medicine tests – namely bone scans, galliumscans and white cell scans, on the other hand, arewidely available, relatively inexpensive, can do whole-body survey for other sites of infection, and are stillconsidered the most sensitive and specific tests forbacterial bone infections, especially if combined withSPECT (Single Photon Emission ComputedTomography) as shown in the table below.

A bone scan is a 2-3 hour test available in all hospi-tal nuclear medicine departments in Canada, and isdone in three phases:

1. Blood Flow or low resolution nuclearangiogram;

2. Blood Pool – or inflammation scan doneimmediately after the flow images as bloodis “pooled” in the capillaries, mostly themuscles and organs, and which correspondsto a low resolution T2 MRI image; and

3. Bone delay images at 1.5-3 hours and corresponds to a “mini-skeleton” showingareas of active bone deposition.

The bone scan is very sensitive and specific forosteomyelitis, and is positive as early as 24 hoursafter infection is suspected when standard x-rays ofthe bones are often negative. However, since it onlysees bone inflammation and “repair”, other condi-tions, such as fracture, tumor, osteoarthritis orrheumatoid arthritis can cause false positives, andcertain areas, such as the spine, which are difficult toevaluate on planar nuclear medicine, can be missedin early osteomyelitis.

Often, the patient history, raised white count, andlater x-ray changes are enough in the presence of apositive bone scan to make the diagnosis ofosteomyelitis. However, in difficult or confusingcases, in order to increase the specificity of the bonescan, other more specific, but also more expensiveand time-consuming, nuclear medicine tests can beadded. The easiest is the 24 hour bone scan – or“four-phase” bone scan, which can occasionally helpin the certainty of increased uptake. However, thetwo most widely available tests in nuclear medicinefor improving sensitivity for bone infection are thegallium scan, using the radioactive tracer Gallium-67, and the labeled white cell scan.

Ga l l ium-67,when injectedinto patients,binds to trans-ferring whichis incorporat-ed into whitecells and bac-

teria. It is widely available in almost all Canadiannuclear departments, quite specific for infection(although it also localizes in certain tumors), and fair-ly inexpensive. However, because it is cyclotron-pro-duced, it usually must be ordered specially for eachpatient, and imaging of gallium is done over 2-4days. Also, because it localizes in all inflammation,the patterns of uptake can be increased even in non-infections,

The other technique in nuclear medicine is to uselabeled white cells, using the patient’s own cells asthe infection-seeking vehicle, with either Tc-99m orIn-111 as the radioactive “tracer”, which follows thecells to the site of infection. This is highly specific forosteomyelitis, although in some cases yet anothernuclear test must be added. This is because labeledwhite cells also target normal marrow, and in somepatients, such as those with infected prostheses, themarrow-expansion resulting from the surgery canconfuse whether the patient has an infection or sim-ply a normal variation resulting from the surgery.One particularly useful area for white cell scanning isin diabetic patients, where because of poor vascular-ity, there is increased risk for infection, particularly inthe peripheral tissues such as the hand and foot.

Diabetics often, however, have peripheral neu-ropathies and Charcot injuries to the feet or hands.In this setting, a bone-scan and white cell scan arefrequently the only way, short of frank pus comingout of the extremity, of making the diagnosis.

In conclusion, nuclear medicine offers a number ofhighly sensitive and specific tests for the presence ofosteomyelitis to Canadian doctors, which are costeffective, widely available, and inexpensive.

34 LE PATIENT Vol. 9, nº 1 LE PATIENT Vol. 9, nº 1 35

NUCLEAR MEDICINE IN THEDIAGNOSIS OF OSTEOMYELITIS

indicates that the pylorus is open and, in that cir-cumstance, a negative lavage would reliably excludean active upper GI bleed and indicate a lower GIbleed.

Radionuclide scintigraphy is an easy non-invasivediagnostic tool to evaluate lower GI bleed, which candetect hemorrhage at rates as low as 0.1 to 0.5mL/min. It does not only detect a bleed but also canlocalize the site of the bleed. This can be done bytwo methods: the “pulse” method using 99mTc sul-phur colloid and the “blood pool” method using99mTc labeled red blood cells. With both of thesetechniques, no preparation is necessary for thepatient.

In the first method, the rapid clearance of the tra-cer from the blood circulation into the reticuloen-dothelial system allows a detection of very lowbleeding rates (0.1 ml/min in animal experiments).The disadvantage with that technique is that itdetects bleeding that only occurs within up to 10minutes after the radiotracer injection, and the

bleeding sites in the upper abdomen may be obscu-red by the intense physiologic accumulation of thetracer in the liver and in the spleen. Using thismethod, imaging begins immediately followinginjection of 99mTc sulfur colloid and dynamicimages are generated over 20 minutes. Once thebleeding site is visualized, additional time must beallowed to see the passage of the tracer and deter-mine whether it is of small bowel or large bowelorigin.

In the second method, 99mTc labeled red blood cellsremain in the vascular space to make continuousmonitoring of the entire GI tract for a long time. Thein vitro technique of labeling RBCs is the preferredmethod to label RBCs over the in vivo and modifiedin vivo techniques because of the highest labellingefficiency. With radionuclide imaging using 99mTclabeled red blood cells, dynamic images are acquiredover 60 minutes initially to allow the identification ofthe bleeding site and the intraluminal motion of thelabeled RBCs. Longer imaging times are possible toincrease the sensitivity for the detection of intermit-tent bleeds and allow sufficient time to see the pas-sage of the tracer and determine whether it is ofsmall bowel or large bowel origin.

Radionuclide imaging requires active bleeding todetect a source and is indicated for severe (highrisk) GI bleed. Patients with intermittent or inac-tive (low risk) bleed can be scheduled for colono-scopy. Difficulty of localization of bleed can occurwith radionuclide imaging, particular with redun-dant transverse or sigmoid colon. However, thisdifficulty can be overcome by obtaining SPECT/CTimaging.

Marc Hickeson, MD, FRCPc

Residency ProgramDirector

McGill NuclearMedicine

Gastrointestinal (GI) bleed refers to any bleedoriginating from the gastrointestinal tract andis a potentially life threatening disorder. It can

be divided into upper and lower GI bleeds. Upper GIbleed occurs proximal to the ligament of Treitz andlower GI bleed occurs distal to the ligament of Treitz.Lower GI bleeds account for approximately 20% ofepisodes of GI hemorrhage and are usually due todiverticular disease, angiodysplasia or, less com-monly, after polypectomy.

An indication of the site of the GI bleed is the colorof the stool. The presence of melena, which isknown as black tarry stools, is indicative of blood

that has been in the GI tract for at least 8 hours. Thepresence of melena indicates that the source ofbleed is much more likely to be in the upper GI tractthan in the lower GI tract. On the other hand, thepresence of hematochezia, which is known as brightred blood per rectum, is indicative that the source ofbleed is much more likely to be from the lower GItract than the upper GI tract. A nasogastric (NG)aspirate can be done to differentiate an upper fromlower GI bleed. The presence of blood in the aspi-rate reliably confirms upper GI bleed. However, anupper GI bleed may be missed if the bleed has stop-ped or arises beyond a closed pylorus. If the NGaspirate shows the presence of bilious fluids, this

LOWER GASTROINTESTINAL BLEED:A FOCUS ON RADIONUCLIDESCINTIGRAPHY


Algorithm for investigation of lower gastrointestinal bleed


Figure 4

Case 4:71 year old patient presented with hematochezia. Radionuclideimaging using RBCs (Figure 5) showed extravasation (small arrow)in the right lower quadrant of the abdomen. SPECT/CT confirmedthat the location of the bleed was in the ascending colon (largearrow) on the maximal intensity projection image (Figure 6A) andtomagraphic images (Figure 6B, 6C and 6D).

Figure 5

Figure 6


Case 1:Radionuclide bleeding study was done using 99mTc sul-phur colloid. Images demonstrated clearance of theradiotracer from the blood circulation into the reticu-loendothelial system (liver, spleen and bone marrow)within 10 minutes after injection. No active bleed wasdemonstrated on that study.

Figure 1

Case 2:71 year old patient presented with bright red blood perrectum. Radionuclide imaging using RBCs (Figure 2)showed extravasation initially in the right side of theabdomen (arrow) at the first minute of the study. Laterimages showed that the distribution of the radiotraceractivity framed the abdomen with the radiotracer pre-sent in the regions of the ascending, transverse anddescending colon.

Figure 2

Case 3:90 year old patient presented with hematochezia.Radionuclide imaging using RBCs (Figure 3) showed

extravasation initially in the left upper quadrant of theabdomen, which tracked inferiorly. SPECT/CT clearlyshowed a convoluted distribution of the tracer in theleft aspect of the abdominal cavity on the maximalintensity projection image (wide arrow, Figure 4A)rather than framing of the abdomen that would beseen in a large bowel bleed.

The tomographic images demonstrated absence ofthe radiotracer throughout the large intestines andrectum, in the descending colon (short arrow, Figures4B1-3, 4C1-3 and 4D1-3) and the radiotracer was inloops of intestines anterior to the descending colon(long arrow, Figures 4B1-3, 4C1-3 and 4D1-3). Thesefindings indicated that the site of the bleed was in thejejunum rather than the descending colon.


Figure 3


When visiting a patient with atypical cogni-tive defects or movement disorder,refractory epilepsy or, during follow-up

of a brain neoplasm, brain imaging studies innuclear medicine might help you to accuratelyevaluate your patient’s disorder.

Cerebral blood flow studies with Ceretec® orNeurolite®, as well as brain metabolism studieswith 18FDG (fluorodeoxyglucose) (table 1) can helpdetermine the cause of dementia (Alzheimer’s dis-ease (AD), fronto-temporal dementia (FTD) ordementia with Lewy body disease (DLBD)) and/or amovement disorder unresponsive to medications(multiple system atrophy, corticobasal degenera-tion or supranuclear palsy). In addition, these sameexams can also help localize an epileptic focus incase of refractory epilepsy. Furthermore, thedegree of glucose hypermetabolism with 18FDGhelps determine the aggressiveness of a tumorand, later on, to evaluate the responsiveness totreatment and to look for recurrence when con-ventional imaging cannot distinguish post-irradia-tion changes from recurrence.

The brain nuclear imaging pos-sibilities are multiple, and this iswithout taking into accountthe possibilities of more specif-ic tracers that could eventuallyreach clinical availability, suchas dopaminergic tracer(Datscan®), tumoral tracer(18FET) or amyloid tracer used indementia diagnosis.

The most frequent and recog-nized use remains dementiaimaging, which will be the sub-ject of this article.

ALZHEIMER’S DISEASE

According to the most recentstatistics, approximately500,000 Canadians suffereither from AD or a similardementia. By 2038, this num-ber will double. Currently, themedications available todecrease or slow down theprogression of cognitive symp-toms are useful only in AD, jus-tifying the need to obtain aprecise diagnosis wheneverpossible before giving suchmedications, which cost is notnegligible. Furthermore, hav-ing the right diagnosis is help-

ful when discussing with families about the diseaseand prognosis.

SPECT VS PET? WHAT IS THE DIFFERENCE?

Depending on different hospitals, two types ofbrain nuclear imaging are available. SPECT (SinglePhoton Emission Computed Tomography) is atomographic test (3 D slices) available in all nuclearmedicine departments since it’s done with conven-tional gamma cameras. It uses a blood flow tracerwith technetium-99m to image brain perfusion.

Brain FDG PET (positron emission tomography) isavailable in different PET centers in Quebec (table1). It uses glucose to study brain metabolism. Withregards to dementia, the bio-distribution of thetwo types of radiotracers is similar. PET studies aresomewhat more accurate, however, when notavailable, SPECT is a good alternative. (Note: tosimplify reading in the following paragraphs, theterm hypometabolism will be used when referringto a PET exam, while the term hypoperfusion willbe used when referring to SPECT).

Nancy Paquet, MD, FRCP(c)

Professeur adjoint,Département de médecinenucléaire et radiobiologie

Directrice, Programme de médecine nucléaire

Université de Sherbrooke

BRAIN IMAGINGIN NUCLEAR MEDICINE

METABOLIC PATTERNS OF DIFFERENTTYPES OF DEMENTIA

Distinguishing AD from FTD is sometimes difficult inclinical routine, especially when a frontal syndromecomplicates the presentation. With nuclear brainimaging, this distinction is usually easy to make. Inearly AD, bilateral parieto-temporal hypometabolism(figure 1B) is seen, often asymmetrical, which willeventually progress toward dorsolateral frontalregions. There will also be an early involvement ofthe posterior cingulate gyrus and precuneus. Byopposition, FTD will show a predominantly bilateralfrontotemporal hypometabolism, most marked intheir frontal aspect (figure 1C). DLBD will showdefects similar to AD, with further extension to theoccipital region (table 2). Vascular dementia is rathera conventional imaging diagnosis, with focal asym-metrical defects that can be seen.

BEFORE PRESCRIBING A BRAIN IMAGING STUDY!

There are confounding factors important to know.For example, uncontrolled hypothyroidism andmajor depressive disorder can cause hypometabo-lism similar to AD. It is thus essential to establishthat TSH is normal before sending your patient fora brain study. Besides, TSH detection is rarely aproblem. Likewise, it is as important to wait for theresolution of a depressive episode to avoid misinter-pretation of the results, necessitating the need torepeat the exam at a later date and, of course,incurring unnecessary costs and stress. This is alsotrue for any psychiatric syndrome. It is also worthmentioning that DLBD and Parkinson’s dementiahave similar metabolic patterns and therefore can-not be distinguished from one another by eitherPET nor SPECT.

In conclusion, when would it be best to request forthese exams? Well, mainly whenever there is uncer-tainty between the diagnosis of AD and FTD. On theother hand, the use of SPECT or PET is not recom-mended when one wants to differentiate DLBD fromParkinson’s dementia, since these have the samemetabolic pattern. Finally, it is imperative to wait forthe resolution of a depressive or psychiatric syn-drome before requesting such tests.

Table 1

Table 2


Figure 1 Transaxial slices and 3D reconstructions of 18FDG PET studies

A-Normal: homogeneous cortical distribution.

B-Alzheimer’s disease: mainly bilateral parieto-temporal hypometabolism.

C-Fronto-temporal dementia:mainly bilateral fronto-temporalhypometabolism.

(much better than with xenon gas) in 3D.Therefore, a probabilistic interpretationof results is totally discarded in favor of abinary interpretation (embolism presentor absent), even though the basis of thediagnosis remains the same: embolism isdeemed present when a vascular typeperfusion defect is ventilated. Figure 1shows a normal exam, while figures 2 to4 show embolism of increasing size.

Available studies show that V/Q SPECTand CTPA have very similar accuracies,with V/Q SPECT being slightly more sen-sitive, but slightly less specific. Besides avery high sensitivity and a negative pre-dictive value over 95%, V/Q SPECT hasseveral benefits over CTPA, namely amuch lower radiation dose, absence ofallergic reactions or contrast nephropa-thy and a more reliable detection of sub-segmental embolism. This profile makesit the imaging test of choice for most ofthe usual indications, especially if thechest X-ray is not severely abnormal.CTPA can be used as a first line study formore complex cases, specifically thosewho would require a chest CT anywayfor a complete evaluation of their symp-toms. CTPA is also a good choice forunstable patients, as it can be completedmuch quicker than a V/Q SPECT. Table 1compares characteristics of V/Q SPECT tothose of CTPA.

In the last few years, concern has beenraised about the radiation dose incurredto patients by the rising use of CT in clin-ical practice. Table 2 compares the radia-tion dose given by both imaging tests. Ascan be seen, dose levels are much lowerfor V/Q SPECT, which is much moreappropriate for widespread use in a largepopulation, including low to moderateclinical probabilities. The dose to thebreasts is very high for CTPA, represent-ing the equivalent of 10-25 mammo-grams. Even if we take into account spe-cial low dose protocols for CTPA, the dif-ference with V/Q SPECT is still substan-tial. Fetal dose is very low for both tests(negligible risk in both cases), but thehigh total and breast doses incurred byCTPA to young mothers make V/Q SPECTa much better option for this group.

When PE is diagnosed, it is important toobtain a follow-up exam three monthslater to assess the degree of reperfusion.This control will also serve as a baselinein case of recurrence and will identifypatients with chronic embolism at risk of

Michel Leblanc MD,RCPSC, ABNM

Chief of Staff, NuclearMedicine Department

Centre Hospitalier AffiliéUniversitaire Régional

de Trois-RivièresClinical professor,

University of MontrealClinical professor,

University of Sherbrooke

Pulmonary embolism (PE) is a frequent andpotentially lethal disease caused by a loosethrombus, originating most frequently from

the lower limbs, migrating to the lungs and caus-ing occlusion of a part of the pulmonary circula-tion. The diagnosis of pulmonary embolism is diffi-cult because no combination of signs and symp-toms is sensitive or specific. Different strategieshave been devised to evaluate the clinical probabil-ity, for example, Wells score. They are usually com-bined with D-Dimer measurements and, if theresultant probability is moderate or high, furtherinvestigation is warranted.

Therefore, imaging tests are often required toestablish the diagnosis. Traditionally, it was mainlybased on planar ventilation and perfusion scintig-raphy (“lung scan”). When it showed one or sever-al areas of poorly perfused but adequately ventilat-ed lung, it was considered compatible with PE.However, because of the high rate of indetermi-nate readings, especially within the PIOPED scheme

of interpretation, it was progressively replaced inmost settings by computerized pulmonary tomo-graphic angiography (CTPA).

Within the last few years, the availability of a high-ly performing nuclear medicine ventilation agent(technegas) enabled the emergence of a majortechnical enhancement, tomographic tridimen-sional analysis of ventilation and perfusion, mainlyknown as Ventilation Perfusion Single PhotonEmission Computed Tomography (V/Q SPECT). Thistechnique has major advantages over traditionalplanar ventilation perfusion imaging.

Using tomographic imaging improves sensitivity forPE and drastically reduces indeterminate readings(< 5% of cases) due to better contrast and 3D visu-alisation of perfusion defects. This enables classifi-cation of defects into vascular or non-vascular ori-gin, with much more accuracy than with conven-tional planar imaging. Matching or mismatching ofventilation with perfusion is easily determined


V/Q SPECT IN PULMONARY EMBOLISM

Figure 1:Normal V/Q SPECT, coronal slices. Note homogenous distribution in both ventilation and perfusion.

Figure 2:Sub-segmental PE. Small typical vascular type perfusion defect with normal ventilation, viewed in triangulation mode (coronal, sagittal and transverse slices).

Figure 3:Large segmental PE. Large typical vascular type perfusion defect with normalventilation, viewed in triangulation mode (coronal, sagittal and transverse slices).


pulmonary hypertension. In case of massive initialembolism, a first follow-up exam is obtained 7-10days after the initial episode, which will serve asprovisory baseline image in case of early symptomrecurrence.

CONCLUSION

V/Q SPECT has superseded traditional planar venti-lation perfusion imaging for the evaluation of pul-monary embolism. It is a highly accurate test thatcan be used as a first line procedure in most usualclinical scenarios.


Figure 4:Extensive PE. Multiple and extensive perfusion defects, both complete

and partial, with normal ventilation.

Table 1: Summary of advan-

tages and limita-tions of CTPA and

V/Q SPECT

Table 2: Summary of typical

radiation dosesincurred from CTPA

and V/Q SPECT(mSv = millisievert)

SCINTIMAMMOGRAPHY AND CANCER OF THE BREAST

There are various goals to breast imaging. In patientswith no known malignancy, breast imaging is per-formed with the aim of early detection of cancer, as

well as assisting in separating benign lesions and prema-lignant or malignant lesions. Morphology of the breast isindividual. It may vary from one patient group to anoth-er, may vary in the same individual during the menstrualcycle and may change with age. So is the risk for malig-nancy and the performance of the different imagingmodalities. Mammography, which is the most readilyavailable screening modality, may be satisfactory inpatients with fatty breasts, but its lesion detect abilitydeteriorates the denser the breast tissue is.

Once breast cancer in diagnosed, imaging of the breast isno longer aimed for screening but is rather diagnostic,assessing the local extent of the disease and monitoringresponse to therapy. Based on the extent of the disease,the patient may be referred for lumpectomy, mastectomy,neo-adjuvant therapy, etc. During the course of the dis-ease, assessment of tumor viability and detection of localrecurrence are common indications for breast imaging.After treatment, morphology of the breast becomes evenmore variable.

The use of MRI (magnetic resonance imaging) has over-come many of the limitations of mammography, evenwhen combined with sonography in screening of high-risk patients and patients with dense breasts, as well asin patients with proven malignancy. But MRI is not


Prof. Einat Even-Sapir WeizerMD, PhDHead, Department of Nuclear MedicineTel Aviv Sourasky Medical CenterSackler School of Medicine, Tel Aviv [email protected]


always the optimal solution. MRI may be less available.There are contraindications for MRI and it may be diffi-cult to perform a study in claustrophobic patients. MRImay be of compromised specificity leading to a high rateof futile biopsies and it is not always sensitive for assess-ment of tumor viability.

In recent years, novel functional techniques, dedicatedfor breast imaging with radiotracers have emerged inclinical practice of breast health. Breast cancer can bedetected on PET, preferably on Positron EmissionTomography (PEM), in places where there are nearbycyclotrons and for FDG-avid tumors.

99Tc-MIBI technetium-99m (Tc-99m) sestamibi is a single-photon emitter tracer routinely used in most depart-ments of nuclear medicine for myocardial perfusionstudies and, therefore, is readily available. It concen-trates in cells with increased mitochondrial density, acommon condition in malignant breast disease. Thistracer was used two decades ago for breast imagingusing the general routine gamma cameras, which aresuboptimal for detection of small tumors in breasts,which are approximately 15 cm from the collimators andup to 25 cm from the region of interest. Currently thereare small breast gamma-cameras designed as organ-specific cameras, including devices composed of theroutine NaI(Tl) detectors (breast-specific gamma imag-ing, BSGI) and MBI – molecular breast imaging devicescomposed of the novel dual-head cadmium zinc tel-luride (CZT) detectors, improving resolution and allow-ing for the detection of smaller lesions.

Using a dual-head cadmium zinc telluride (CZT) detec-tors cameras (Molecular Breast Imaging, MBI),researchers in the Mayo clinic have found small malig-nant lesions of 3 mm and calculated a sensitivity of 90%in tissue abnor malities, with diameters of 5 mm to 20

mm. Screening 936 at-risk women, Rhodes et al of theMayo Clinic reported that the sensitivity of mammogra-phy alone for these difficult-to-image patients was27%, while the sensitiv ity of combined mammographyand MBI was 91%. Recently at the RSNA, the group inMayo Clinic have reported good performance of MBIwith low-dose Tc-99m sestamibi of 8mCi having anongoing dose-reduction work aiming to perform MBIwith 4 mCi Tc-99m sestamibi, with an effective dosecomparable to a screening mammogram.

18 months ago, an MBI system (Discovery* NM750b, GEhealthcare) has been installed in the department ofNuclear Medicine at the Tel Aviv Medical Center. Weapproached our clinicians; breast surgeons and oncolo-gists as well as breast radiologists, conducting researchaimed at understanding the potential complementary roleof MBI. We offered the physicians to refer for MBI womenin whom it was felt that additional non-invasive imagingwas clinically indicated. In addition to patients with nomalignancy but highrisk for cancer, dense breast orequivocal breast imaging, over 100 patients with alreadyproven cancer were referred, assisting in building a rangeof indications for the use of MBI as a breast diagnosticmodality. These indications included determining theextent of disease in patients referred for lumpectomy inwhom clinically, or on other imaging, the possibility ofmore extensive disease could not be ruled out, patientsprior to and post neo-adjuvant therapy, assessing thepresence of viable tumor tissue post-surgery and patientswith axillary metastatic lymph node spread and occult pri-mary. Sensitivity of MBI in these complicated cohorts was88%. Causes for false negative were lowgrade DCIS,microscopic remnant disease after treatment and lactat-ing breast within a week from delivery. In patients whohad MRI, MBI and MRI resembled for the majority of pre-malignant and malignant lesions. These preliminary find-ings encourage further accumulation of data.

Pub GE

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