Diagnosis No. of cases

31

Frank H. Deland, A. Everette James, Jr., Henry N. Wagner, Jr., and Fazle Hosain

Johns Hopkins Medical Institutions, Baltimore, Maryland

Although the cerebrospinal fluid (CSF) is probably formed in many regions of the subarachnoidspace, the bulk of CSF is produced in the choroidplexuses of the third and lateral ventricles (1 ) . Thenormal direction of flow is from the ventricular systern into the subarachnoid spaces surrounding thebrain stern, spinal cord, and brain, finally concentrating in the parasagittal area. For radionuclide cisternography the radiopharmaceutical is usually introduced into the lumbar intrathecal region and fromthis point the activity can be followed from the spinalcanal to the parasagittal regions where it is absorbed.

On the basis of the relatively constant flow patternof cerebrospinal fluid, radionuclide cisternographyreflects:

1. The movement of spinal fluid through the subarachnoid space.

2. Absorption of spinal fluid from the cerebro

spinal spaces into the vascular and extravascular spaces (2—6), and

3. Entry and exit of spinal fluid into or from theventricular system under pathologic circurnstances.

In the past 12 months we have performed 12Scisternograms using 169Yb-Ca-diethylenetriaminepentaacetic acid (DTPA) as the radiopharmaceuticalat the Johns Hopkins Medical Institutions. This report summarizes our experience with the use of thisradiopharmaceutical for cisternography.

METHODS

In the majority of cases, the radiopharmaceuticalwas injected into the lumbar intrathecal space. Radionucide images of the brain were routinely performedin the anterior, posterior, and both lateral positions.When indicated, vertex views were obtained as wellas other views such as the spinal region or abdomenwhen dictated by the specific requirements of thepatient. Routinely examinations were performed at2, 6, and 24 hr, and when the early images failedto show normal movement to the parasagittal region,delayed studies at 48—96hr were also obtained.

Table 1 summarizes the clinical categories that westudied using 169Yb-DTPA.

The diagnosis of these cases as normal, normalpressure hydrocephalus, cerebral atrophy, shunts,etc., was established in all cases by clinical history,radiological studies, surgery, or postmortem examination.

RESULTS

Figure 1 shows a normal cisternogram performedat 2, 6, and 24 hr after the lumbar intrathecal injection of 169Yb-DTPA. At 2 hr after injection (Fig.1A) the radiopharmaceutical has migrated into theinfratentorial cisterns and entered the Sylvian fissures.The tentorial limit of the posterior fossa is well illustrated in the posterior view. By 6 hr (Fig. 1B) theactivity has flowed through the Sylvian fissures and isseen over and between the cerebral hemispheres.

Activity is still present in the cisterns beneath thetentorium at this time but is decreased in concentration compared with the 2-hr study. Twenty-four hoursafter injection (Fig. I C) the radiopharmaceutical ispredominantly over the cerebral hemispheres andis concentrated in the parasagittal region. There islittle activity remaining in the posterior fossa.

Table 2 summarizes the average distribution of

Received Dec. 22, 1970; revision accepted April 27, 1971.For reprints contact: Frank H. DeLand, Div. of Nuclear

Medicine, University of Florida, Gainesville, Florida.

TABLE1. RESULTSOF 125 CISTERNOGRAMS

Normal“Normalpressure―hydrocephalusCerebral atrophy with hydrocephalusSurgical shuntsPartial obstruction to CSF flowTotal obstruction to CSF flowCSF leaksUnsatisfactory

25261810258

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DELAND, JAMES, WAGNER, AND HOSAIN

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684

seen over and between cerebral hemispheres.C shows normal cisternogram 24 hr after lumbar intrathecal injection. Radioactivityis predominately over hemispheresand concentrated in parasagittal region.

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in basal cisterns and lateral ventricles. C shows normal pressurehydrocephalus 24 hr after injection when activity has migrated intoSylvian fissures. Failure of migration of radionuclide over cerebralconvexities is clear.

Volume 12, Number 10 685

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DELAND, JAMES, WAGNER, AND HOSAIN

the radionuclide in 3 1 normal patients for eachperiod of the examination.

Figure 2 is an example of normal pressure hydrocephalus. Two hours after intrathecal lumbar injection (Fig. 2A) radioactivity has migrated into thebasal cisterns and lateral ventricles. At 6 hr after injection (Fig. 2B) there has been little movement ofthe radiopharmaceutical. By 24 hr (Fig. 2C) activityhas migrated into the Sylvian fissures and slightlyover the convexities. The region with the greatestconcentration of activity is still the lateral ventricles.Table 3 summarizes the average distribution of activity in 25 patients with normal pressure hydrocephalus.

Figure 3 illustrates the cisternogram seen in apatient with primary cerebral atrophy. Two hoursafter intrathecal lumbar injection (Fig. 3A) theradiopharmaceutical has migrated into the basal cisterns and slightly into the Sylvian fissures. The nuclide images appear very similar to the normal cisternogram at the same interval. In Fig. 3B the imagesare quite similar to a normal cisternogram performed6 hr after injection although these images were made24 hr after injection of the radiopharmaceutical,

demonstrating marked delay in movement. At 48 hrafter injection (Fig. 3C) the activity is concentratedover the hemispheres and in the parasagittal region.Again, scintigrams are typical of those performed ina normal patient 24 hr after injection. Table 4 summarizes the distribution of activity in 26 patientswith primary atrophy.

Figure 4 is an example of a partial obstruction toflow of injected radiopharmaceutical over the righthemisphere following head trauma in a patient witha suspected spinal fluid leak. This cisternographicpattern indicates that although a localized area of

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FIG. 3. Cerebral atrophy. Movement of radionuclide appearsnormal except for time required: A—2hr after injection, B—24hr,and C—48 hr.

TABLE2. DISTRIBUTIONOF 16tIYb@DTPAINNORMAL PATIENTS

(INTRATHECALLUMBARINJECTION)

Time after intrathecal injection

2hr 6hr 24hr

Mean Range Mean Range Mean Range

+ + +—to+— —+ + + + —or+—to+

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Basal cisternsSylvian cisternsVentriclesConvexitiesParasagittal

+ indicatessignificantconcentrationof radioactivity.— indicates little to no activity.

sI indicates slight activity; the numerical fractions indicatethe distance over the cerebral hemispheres between thesylvian fissures and the superior sagittal sinus.

TABLE3. DISTRIBUTIONOF ‘6°Yb-DTPAINCASESOF NORMALPRESSUREHYDROCEPHALUS

(INTRATHECALLUMBARINJECTION)

Time after intrathecal injection

2hr 6hr 24hr

Mean Range Mean Range Mean Range

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+ indicatessignificantconcentrationof radioactivity.— indicates little to no activity.

SI indicates slight activity.mod indicates moderate activity.The numerical fractions indicate the distance over the

cerebral hemispheres between the sylvian fissures and theparasagittal sinus.

TABLE4. DISTRIBUTIONOF 1°9Yb-DTPAINCASESOF CEREBRALATROPHY

(INTRATHECALLUMBARINJECTION)

Time after intrathecal injection

2hr 6hr 24hr

Mean Range Mean Range Mean Range

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cerebral hemispheres between the sylvian fissuresand theparasagittal sinus.

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FIG. 5. Partialobstructivearachnoiditisover left cerebralhemisphere. Radioactivity has entered lateral ventricles indicatinginadequate absorption of CSF.

FIG. 4. Partialobstructivearachnoiditisover left cerebralhemisphere. Absorption of CSF appears adequate since radionuclide does not enter lateral ventricles.

adhesive arachnoiditis is present, absorption of CSFis still adequate since there is no entry of radioactivity into the lateral ventricles. By contrast Fig. 5is an example of a partial obstruction to flow dueto an adhesive arachnoiditis with entry of the radionudide into the lateral ventricles. In this case whichwas due to subarachnoid hemorrhage, absorption ofCSF is altered and ventricular dilation is present.The patient's symptoms were alleviated by a yentriculoatrial shunt. In Fig. 6 there is complete obstruction to flow at the level of the tentorial notch ina patient with Paget's disease of bone. The obstruction is probably due to basal arachnoid thickening.

Figure 7 illustrates the rapid excretion of 169YbDTPA from the vascular pool in a patient with a

functioning ventriculoatnal shunt. The radiopharmaceutical was introduced into the lumbar intrathecalspace, migrated to the lateral ventricles, and thenmigrated into the shunt. The activity was extractedfrom the blood by glomerular ifitration and can beseen in the kidneys, urinary bladder, and catheter.

Figure 8 shows a CSF leak through the cribiformplate and obstruction to flow over the right hemispheres. At 7 hr after lumbar intrathecal injection,activity has migrated anteriorly into the nasopharyngeal area (lateral view) , and a localized area of activity has accumulated in the nose.

DISCUSSION

The characteristics of a good cisternographic radiopharmaceutical are high photon yield for images ofgood resolution, adequate effective half-life for extended studies beyond 24 hr, acceptable radiation

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DELAND, JAMES, WAGNER, AND HOSAIN

dose, biological safety, photon yield of an appropriate@@ •1gamma for available instrumentation, and acceptable Iavailability and cost. Certain of the biological, chemical, and physical properties make ‘69Yb-DTPAa@desirable radiopharmaceutical. Experimental studieshave shown that the effective half-life of 169Yb-DTPAin the subarachnoid space is 10—12hr. Although themolecular weight of 161tYb-DTPA is 600, it demonstrates generally the same pattern of movement inthe CSF as albumin and appears to be resorbed from -the CSF space in the parasagittal region (arachnoidgranulations) . Once 169Yb-DTPA has entered the@ Ivascular pool, it rapidly equilibrates with the extracellular fluid space and is then excreted in the urine.@ IWith normal renal function, 60—70% of an intra-@@ ,

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FIG. 8. Cerebrospinalfluidleak.Migrationof theradionuclideinto the nasopharynxand nose (N).

venous dose appears in the urine in the first 2 hrand 99% of the injected dose is excreted in the urinein 24 hr (7,8). In patients with normal glomerularfunction the radiation dose compares favorably withthe most common radiopharmaceutical used for CSFimaging, 1311-IHSA (9). The yield of 63 X 10°useful photons/rad whole-body dose characterizes‘°°Yb-DTPAas a high photon-yield radionuclidewith a long shelf-life (T,,2 = 32 days). We wouldcaution against the use of this radiopharmaceuticalin patients with reduced glomerular function.

169Y@DTPA is administered in doses of 1 mCi foran adult patient, and this photon yield is adequatefor images of high resolution. In comparing thesestudies with those obtained with 131I-IHSA the majordifference appears to be better resolution of anatomical detail, particularly in delayed studies (48—96 hr).In those patients with obstruction to normal CSFflow, delayed studies are very valuable (10). This isparticularly true in differentiating hydrocephalus dueto abnormal absorption of spinal fluid (normal pres

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sure hydrocephalus) and hydrocephalus due to primary brain atrophy from patients with normal flowpatterns seen with radionuclide cisternography. Thusit is desirable that the effective half-life of the radiopharmaceutical be adequate for studies in excess of24 hr, i.e., 48—72 hr. The 32-day physical half-lifeof 169Yb insures adequate photons for extendedstudies, yet the biological half-life ( 12 hr) is shortenough to provide adequate safety regarding radiation dose.

For imaging, the I 77- and I 98-keV gamma emission are detected. Their fractional abundance is relatively high (0.6 photon/disintegration) and excellentimages can be obtained using a 160—220-keVwindow. Only a small fraction (10% ) of the gammaemissions is above 198 keV, thus allowing imagingon both camera and rectilinear scan devices.

Ytterbium complexes with diethylenetriaminepentaacetic acid to form a stable compound. Three ofthe five bonds of the DTPA chelate are taken up bythe ytterbium; the remaining two are taken up bythe calcium which is added to prevent calcium depletion of the cerebrospinal fluid. The preparation of160YbDTPA for cisternography is described in another publication (9).

The bond between 169Yband DTPA is very stableand therefore provides a good shelf-life. Equallyimportant, the long shelf-life permits thorough testingfor sterility and pyrogenicity. As we have shown,there was no tissue reaction found in experimentswith laboratory animals (9). Ytterbium-l69-DTPAhas many advantages for cisternography (1 1 ) . Ofprime importance is the fact that it can be furnishedready for use, thus obviating any necessity for localpreparation. This radiopharmaceutical has been usedin our laboratory in over I 25 patients, and no ad

verse patient reactions have been observed. Theradionuclide images are of excellent quality, andextended studies up to 108 hr after injection havebeen performed.

ACKNOWLEDGMENT

We would like to thank Miss Wendy North for her effortsand skill in the preparation of this manuscript and the illustrations.

REFERENCES

I. BERING EA: Circulation of cerebrospinal fluid. I Neurosurg19:405—414,1962

2. ATKINSON JR, FOLZ EL: Intraventricular RISA as adiagnostic aid in pre- and post-operative hydrocephalus.I Neurosurg19: 159—166,1962

3. DICHIRO G : Movement of cerebrospinal fluid in human beings. Nature 204 : 290—291,1964

4. DICHIRO G : Observations on the circulation of cerebrospinal fluid. Acta Rad Scand 5: 988—1002,1966

5. BROCKELHURSTG : Use of radio-iodinated serum albumin to study CSF flow. I Neurol Neurosurg Psychiat 31:162—168,1968

6. JAMESAE, DELANDFH, HODGESFJ, Ct al: CSFimaging. Anatomical considerations. Amer I Roentgen 110:74—87,1970

7. H0sAIN F, REBA RC, WAGNER HN: Measurement ofglomerular filtration rate using chelated ytterbium 169. mtI App! Radiat20: 517—521,1969

8. HOSAINF, REBARC, WAGNERHN : Ytterbium 169diethylenetriaminepentaacetic acid complex : A new radiopharmaceutical for brain scanning. Radiology 91 : 1199—1203,1969

9. WAGNER HN, HOSAIN F, DELAND FH, et al: A newradiopharmaceutical for cisternography: chelated ytterbium169.Radiology95: 121—126,1970

10. JAMES AE, DELAND FH, HODGESFJ, et al: Normalpressure hydrocephalus : The role of cisternography in diagnosis.JAMA 213: 1615—1622,1970

11. JAMES AE, DELAND FH, REBA RC, et al: ‘@YbDTPA: A versatile radiopharmaceutical. I Can Rad Assoc,in press

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