Technologic Applications in Technologic Applications in Nuclear Molecular ImagingNuclear Molecular Imaging

Arif Sheikh, MDArif Sheikh, MDAssistant ProfessorAssistant Professor

Director of Targeted Radionuclide TherapyDirector of Targeted Radionuclide Therapyand Cardiovascular Nuclear Medicineand Cardiovascular Nuclear Medicine

Divisions of Nuclear and General MedicineDivisions of Nuclear and General MedicineDepartments of RadiologyDepartments of Radiology

and Internal Medicineand Internal Medicine University of North Carolina University of North Carolina

What Information does an Image Convey?

• Importance of image information

• Unique information portrayed

• Clinical relevance of imaging

• Understanding of technology behind the image

Issues with Nuclear Imaging• Nuclear Imaging

» Low resolution scans» High physical sensitivity

studies» Rely on observation of

physiology» Creates pictures from

individual photon counts

» Low target to background ratio

» Poisson statistics

• Other Radiologic Imaging» Higher resolution» Anatomic pathology

readily visible» Sensitivity is lower than

Nuclear Imaging» Uses ‘energy spectra’

to create images» High target to

background ratio» Gaussian statistics

History of Radiologic Imaging• Historically, much of modern diagnostic imaging was

performed by Nuclear Medicine» Neuro (Stroke) Brain scan → CT, MRI

» Cardiac (Functional) MUGA → Echocardiography (ultrasound)

» Pulmonary (Embolic Disease) V/Q → CT Angiography

» Gastrointestinal• Gallbladder (HIDA) → Ultrasound, CT, MRI• Liver/spleen (Metastases) → CT, MRI

» Genitourinary (Torsion) Testicular Scan → Ultrasound

• Despite advancements, many of these procedures are still used today!

Important Milestones in Nuclear Imaging

• Imaging» Initially, monitored

uptake over body» Anger Camera (image

generation)» Dynamic imaging» Gating» Tomographic (SPECT)

imaging» PET imaging» Attenuation Correction» CT based correction

• Other technologies» Processing

• Filtered back projection• Iterative reconstruction• Scatter correction• Resolution recovery

» Crystals• Sodium Iodide (SPECT)• BGO, LSO, etc. (PET)

» Computer processing• Film uses• Digital displays

Applications in Nuclear Medicine

• Wide range of applications (most versatile as a single imaging system)

• Essentially, evaluates pathology based on functional imaging

• Use of physiologic principles to guide surgeries

• Identification of tissue type based on molecular and/or physiologic parameters

Wide Variations of Nuclear Images

• Image appearance depends upon radiopharmaceutical characteristics• Normal image depends upon the physiologic distribution of tracer• Identification of pathology depends upon deviation from base image

Planar vs. SPECT Anger Camera Images

• Planar Imaging» Better counts

» Improved resolution

» Improved physical sensitivity

» Ability to do dynamic images

» Performed much quicker than SPECT imaging

• SPECT Imaging» Better contrast

» Improved clinical sensitivity

» Tomographic (3-dimensional) views of target region

Bone Imaging

Planar vs. SPECT vs. PET

Frontal view of thyroid

NodulesR L

Field of view of image detector

Thyroid Gland

Pinhole Imaging

Copyright restrictions may apply.

Mandel, S. J. JAMA 2004;292:2632-2642.Mandel, S. J. JAMA 2004;292:2632-2642.

123I Scans of Hyperfunctioning Thyroid Nodules

With suppression of extranodular thyroid

Without suppression of Extranodular Thyroid

Renal Scanning

Resolution vs. Sensitivity

Gated Slice Display

Surgical Mapping Theory• Certain cancers (melanoma, breast, etc.) tumours

may sit in lymph nodes undetected at time of initial diagnosis/surgery

• Tumours spread/metastasize through lymphatic channels

• Detection of tumours in lymph nodes will alter therapeutic approach

• Need to detect specific lymph nodes in entire basins which likely have disease

• Need to be accurate enough to minimize chance of ‘missing’ the target (sentinel) lymph node

Sentinel Lymph Node Mapping• Sentinel Lymph Node (SLN) is the 1st node

to which the tumour will likely metastasize• Detection and examination of this lymph

node will decide whether disease has spread

• Use particles that will travel in lymphatic channels from the tumour to the local lymph nodes to the sentinel lymph node

• Sulfur colloid (~0.1-1 m) particle is taken up by lymph nodes

infraclavicularinfraclavicular

apicalapicallaterallateral

parasternalparasternal

subareolarsubareolarplexusplexuscross-cross-drainagedrainage

from thoracic wallfrom thoracic wall

pectoralpectoral

subscapularsubscapularcentralcentral

to abdom.to abdom.wallwallsubcutaneoussubcutaneous

plexusplexus

Malignant Melanoma of the Back

rightrightgroingroin

rightrightaxillaaxilla

leftleftaxillaaxilla

rightrightaxillaaxilla

leftleftaxillaaxilla

Dual Isotope Imaging• Prostascint® is a

tracer to detect prostate cancer

• 111In based, targets tumour sites

• Also large amount of blood pool activity

• 99mTc-RBC distribute in blood pool, helping distinguish vessels from lymph node uptake

18F +

-

p

PET Principle

PET vs. SPECT• PET

» Improved spatial resolution (clinically)

» Inherent attenuation correction

» Can ‘quantitate’ biologic phenomenon easily

» Isotopes more biologically relevant

• 11C, 13N, 15O• Newer molecular tracers

» Dynamic tomographic images possible

» Shorter imaging times

• SPECT» Better count sensitivity» Ability for simultaneous

multi (dual) isotope imaging

» Wider range of pharmaceutical chemistries

» Isotopes (currently) more readily available

» Less cost (currently)

Prostate Cancer

Transverse Coronal Saggital

DG: 57 years old with High DG: 57 years old with High Grade; local resection, now Grade; local resection, now mass post-RT. Recurrence? mass post-RT. Recurrence? Pelvic Exent. possible?Pelvic Exent. possible?

SPECT SestaMIBI (Rest-Stress)

StrStr

RstRst

StrStr

RstRst

StrStr

RstRst

StrStr

RstRst

Mount Sinai School of Medicine

82Rb-PET Study (Rest-Stress)

Stress

Rest

Stress

Rest

Stress

Rest

Stress

Rest

Mount Sinai School of Medicine

Thyroid Cancer

Metastasis localized to the posterior vertebral bodyMetastasis localized to the posterior vertebral body

Advances in Processing:FBP vs. OSEM (Iterative)

• A major reason for the rise in popularity of PET imaging

• Improved diagnostic abilities• Algorithms were once not

possible due to limitations in computing power

• Optimal algorithms need to account for many variables» The type of camera» Radioisotope» Attenuation Correction (CT

vs. rod sources)» Counts/pixel

Quantitative Imaging• Counts per pixel are a representation of a physiologic

process• Change in process over time allows quantitative analysis

to examine physiologic phenomenon• Quantitation may be imaging based, or simply on counts

(eg. blood samples, urine collections, etc.)• Collection based studies

» Urea breath test for Helicobacter pylori

» Schilling’s test for B12 deficiency

» Calculation of Glomerular Filtration Rate with 125I-iodothalamate

Camilleri M. N Engl J Med 2007;356:820-829

Patterns of Gastric Emptying in Healthy People and in Patients with Diabetic Gastroparesis

MUGA Scans

Image Based Dosimetry

dttAA voxvox ~

Time-activity curveTime-activity curve

Time (d)Time (d)

ÃÃvoxvox

AAvox vox ((tt))

rad

ioac

tivi

ty (

MB

q)

rad

ioac

tivi

ty (

MB

q)

0 1 2

Day1

Day2

Day0

Cumulated activity

124I-Iodine in Thyroid Cancer

61.89 Gy/GBq

54.86 Gy/GBq

33.78 Gy/GBq

Technical Developments

• Multipinhole SPECT• Procedure specific cameras• Advances in OSEM algorithms• Newer detector materials• Radiopharmaceuticals• Transition to ‘Molecular Imaging

The D-SPECT Difference

BROADVIEWTM Technology

• 9 solid state detectors

10X the sensitivity

Twice the resolution

• Each detector can look at 100’s to 1000’s of different angles

• Each detector is independently addressable

Patient 510- Stress/Rest

Conventional D-SPECT, Spectrum Dynamics

Biologic vs. Technologic Challenges

• Ultimately, Biology trumps technology• Newer focus is development of better tracers for

evaluation of biology• Technology is developing to better allow for newer

tracer imaging• Thus, the field of ‘Molecular Imaging’ is

developing» Disease specific tracers» Multiple different tracers to look at the same disease

Papillary Thyroid CaFDG-PET versus 131I scans

FDG vs 124I in Thyroid Cancer

PET-PET-124124IIPET-FDGPET-FDG

FDG Prognosis of Distantly Metastatic Disease (Thyroid Ca)

Wang W et al: Prognostic value of [18F]fluorodeoxyglucose positron emission tomographicWang W et al: Prognostic value of [18F]fluorodeoxyglucose positron emission tomographicscanning in patients with thyroid cancer. J Clin Endo Metab 2000 85:1107-13scanning in patients with thyroid cancer. J Clin Endo Metab 2000 85:1107-13

SPECT-CT (111In-Octreotide)vs PET-CT (FDG)

Patient with rising calcitonin, undetected source on anatomic imaging or octreoscan

SPECT-CTSPECT-CT PET-CTPET-CT

Wilex Renal Cell Carcinoma Wilex Renal Cell Carcinoma 124124I-cG250 Clinical Imaging TrialI-cG250 Clinical Imaging Trial013-004 (CG July 7 Clear cell Fuhrman 2)013-004 (CG July 7 Clear cell Fuhrman 2)

Benign

Gene Imaging

HSV1-tk

Mammalian-tk

124I-FIAU

X

124I-FIAU-PO4

124I-FIAU

FIAU (2'-fluoro-2'-deoxy-5'-iodo-1-FIAU (2'-fluoro-2'-deoxy-5'-iodo-1-ββ-d-arabinofuranosyluracil)/-d-arabinofuranosyluracil)/Thymidine Kinase Thymidine Kinase

HSV1-TKHSV1-TK

TKTK

DPKDPK TPKTPK

[*I]-FIAU[*I]-FIAU

[*I]-FIAU[*I]-FIAU

[*I]-FIAU-(PO[*I]-FIAU-(PO44))

Reporter GeneReporter GeneHSV1-tkHSV1-tk

RadiolabeledRadiolabeledProbeProbe

Gene DeliveryGene Delivery

mRNAmRNAHSV1-tkHSV1-tk

Paradigm for Imaging the Expression of a Reporter GeneParadigm for Imaging the Expression of a Reporter Gene

EnzymeEnzymeHSV1-HSV1-

TKTK

Summary• Nuclear Imaging relies on a vast array of

technologies in the creation and evaluation of imaging

• Technological advancements are important, but still secondary to biological understanding of disease

• Important development of the field moving from physiologic processes to Molecular Imaging

• Molecular Imaging promises to play an important part of future Medical Imaging

• Paradigm shift into the development of personalized medicine