Measurement of regional cerebral blood flow with123I-IMP using one-point venous blood sampling and causality analysis: Evaluation by comparison with conventional continuous arterial blood sampling

OBJECTIVE: Arterial input function represents the delivery of intravascular tracer to the brain. The optimal setting of this function is essential for measuring regional cerebral blood flow (rCBF) based on the microsphere model using N-isopropyl-4-[123I]iodoamphetamine (123I-IMP), in which the arterial 123I-IMP concentration (integral value) during the initial 5 min is usually applied. We developed a novel method in which the arterial 123I-IMP concentration is estimated from that in venous blood samples. METHODS: Brain perfusion SPECT with 123I-IMP was performed in 110 patients with disorders of the central nervous system. A causality analysis determined the relationship between various SPECT parameters and the ratio of the octanol-extracted arterial radioactivity concentration during the first 5 min (Caoct) to the octanol-extracted venous radioactivity concentration at 27 min after an intravenous injection of 123I-IMP (Cvoct). The Caoct/Cvoct value was estimated using various SPECT parameters and compared with the directly measured value. RESULTS: The measured and estimated values of Caoct/ Cvoct (r = 0.856, n = 50) closely correlated when the following 7 parameters were included in the regression formula: radioactivity concentration in venous blood sampled at 27 min (Cv), Cvoct, Cvoct/Cv, and 4 parameters related to cerebral tissue accumulation that were measured using a four-head gamma camera 5 and 28 min after 123I-IMP injection. Furthermore, the rCBF values obtained using the input function estimated by this method also closely correlated with the rCBF values measured using the continuous arterial blood sampling (r = 0.912, n = 180). CONCLUSION: These results suggest that this method would serve as a convenient and less invasive method of rCBF measurement in the clinical setting.     

Evaluation of the 123I-IMP Patlak plot method using the pulmonary differential curve as an input function: a comparison with cerebral blood flow (CBF) determined by the noninvasive micro-sphere (NIMS) method

We explored the possibility of applying the Patlak plot method to clinical practice as a simple non-invasive quantitative method of measuring cerebral blood flow using N-isopropyl-4-[123I]iodoamphetamine (123I-IMP). On the assumption that after temporarily accumulating in the lungs, all the administered 123I-IMP is eliminated by the pulmonary arterial flow for systemic diffusion, we collected dynamic data by setting an area ranging from the brain to the whole lung field within the field of the camera. The lung clearance curve L(t) was differentiated and divided by cardiac output. It was then converted a positive number by multiplying it of--1 to determine the volume of 123I-IMP tracer diffused in arterial blood per unit of time. The calculated concentration was defined as the arterial time activity curve A(t). A Patlak plot analysis was conducted between A(t) and the brain time activity curve B(t) to determine K1 (total cerebral blood flow [tCBF], ml/min) and Vn (nonspecific initial distribution volume, ml). The total volume of tracer diffused in the central cardiovascular system within a given (T) was also obtainer from the volume of tracer remaining in the lungs [Lpeak--L(T)], and by reporting this calculation over time, an accumulation curve was produced. By differentiating the obtained accumulation curve, we were able to estimate the volume of tracer diffused in the central cardiovascular system per unit of time. With this value used as the input function index I(t), a Patlak plot analysis was conducted to determine the unidirection influx index ki, which was then multiplied by 100 to obtain the brain perfusion index (IMP-BPI). The noninvasive micro-sphere method was performed concurrently on 16 patients with cerebrovascular and/or neurological disorders to obtain mean cerebral blood flow (mCBF). Correlations between K1 and between IMP-BPI and mCBF were then determined and compared. Both K1 and IMP-BPI obtained from ki were found to correlate highly with mCBF, r = 0.759 (y = 0.032x + 20.1) and r = 0.833 (y = 2.73x + 0.10) respectively, with a better result from IMP-BPI. These results indicate that the 123I-IMP Patlak plot method with a wide-field gamma camera is clinically applicable as a simpler noninvasive technique for measuring cerebral blood flow even when a simple input function is used.     

Development of a simple method for the washout correction of 123I-IMP SPECT and its application to a quantitative rCBF method

We have developed a simple method to correct the washout of tracer from the brain based on the two-compartment model in brain early SPECT using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). This correction was applied to a new quantitative method of regional cerebral blood flow (rCBF) in combination with the microsphere method by continuous arterial sampling previously reported. Data acquisition of 123I-IMP early SPECT was started from 35 min after 123I-IMP i.v. injection, and the time activity curve of whole brain on anterior head planar images was monitored immediately after 123I-IMP i.v. injection for the correction of washout of tracer from the brain. The usefulness of this method was evaluated in 12 patients with various brain diseases by comparison with the results obtained from the super-early SPECT at 7-10 min after 123I-IMP i.v. injection. The washout rates in cases of early SPECT corrected by this method ranged from 16.91% to 39.34% with a mean +/- SD of 27.72 +/- 5.44%. The contrast of hypo- to hyperperfusion regions on early SPECT was improved by the correction of the washout, and its intracerebral distribution was similar to the simultaneously obtained super-early SPECT images. These results indicated that the present correction method for the washout was useful for more correct quantification of rCBF.     

Database of normal human cerebral blood flow measured by SPECT: II. Quantification of I-123-IMP studies with ARG method and effects of partial volume correction

The limited spatial resolution of SPECT causes a partial volume effect (PVE) and can lead to the significant underestimation of regional tracer concentration in the small structures surrounded by a low tracer concentration, such as the cortical gray matter of an atrophied brain. The aim of the present study was to determine, using 123I-IMP and SPECT, normal CBF of elderly subjects with and without PVE correction (PVC), and to determine regional differences in the effect of PVC and their association with the regional tissue fraction of the brain. METHODS: Quantitative CBF SPECT using 123I-IMP was performed in 33 healthy elderly subjects (18 males, 15 females, 54-74 years old) using the autoradiographic method. We corrected CBF for PVE using segmented MR images, and analyzed quantitative CBF and regional differences in the effect of PVC using tissue fractions of gray matter (GM) and white matter (WM) in regions of interest (ROIs) placed on the cortical and subcortical GM regions and deep WM regions. RESULTS: The mean CBF in GM-ROIs were 31.7 +/- 6.6 and 41.0 +/- 8.1 ml/100 g/min for males and females, and in WM-ROIs, 18.2 +/- 0.7 and 22.9 +/- 0.8 ml/100 g/min for males and females, respectively. The mean CBF in GM-ROIs after PVC were 50.9 +/- 12.8 and 65.8 +/- 16.1 ml/100 g/min for males and females, respectively. There were statistically significant differences in the effect of PVC among ROIs, but not between genders. The effect of PVC was small in the cerebellum and parahippocampal gyrus, and it was large in the superior frontal gyrus, superior parietal lobule and precentral gyrus. CONCLUSION: Quantitative CBF in GM recovered significantly, but did not reach values as high as those obtained by invasive methods or in the H2(15)O PET study that used PVC. There were significant regional differences in the effect of PVC, which were considered to result from regional differences in GM tissue fraction, which is more reduced in the frontoparietal regions in the atrophied brain of the elderly.     

New quantification of regional cerebral blood flow measurements by 123I-IMP SPECT with the rotating gamma camera--theory and validation of the look-up table method]

A new method of quantifying regional cerebral blood flow (rCBF) measurements by N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT with a rotating gamma camera was designed. By assuming the 2 compartment model of the kinetic for 123I-IMP, two parameters of rCBF and distribution volume (Vd) of 123I-IMP from brom brain tissue to blood were obtained by the look-up table method and were derived from two simultaneous equations of the early and delayed images. The rCBF values of 3 cases (two normal adults and one brain infarct patient) were calculated by this method and were compared with the values of positron emission tomography (PET) measured at the same time. The average rCBF values in gray and white matter by this method were 40 ml/100 g/min, 27 ml/100 g/min, respectively and correlated significantly to rCBF values by PET (r = 0.598 (p less than 0.001)).     

The diagnostic value of 123I-IMP SPECT in non-Hodgkin's lymphoma of the central nervous system.

N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT is of low diagnostic value in patients with brain tumors, because brain tumors are visualized as uptake defects. Some reports have described non-Hodgkin's lymphoma of the central nervous system (CNS) as showing high uptake on delayed 123I-IMP SPECT images, suggesting its usefulness in diagnosing CNS lymphoma. In this study, we investigated the clinical value of 123I-IMP SPECT as a diagnostic tool for CNS lymphoma. METHODS: Ninety-six patients with brain tumors, including 12 patients with CNS lymphoma, underwent 123I-IMP SPECT. Eleven patients had primary CNS lymphoma, and 1 had a parenchymal brain metastasis from a breast lymphoma. The total number of lesions was 18, 14 of which were in the cerebral parenchyma, 3 in the brain stem, and 1 in the ventricle. Early SPECT images were initiated 15-30 min after intravenous injection of 111 MBq 123I-IMP, and delayed images were collected 4 h later. SPECT images were visually analyzed with a color-grading scale. Tumor-to-normal activity ratio (T/N) and tumor-to-cerebellum activity ratio (T/C) were calculated for both early and delayed images for semiquantitative analysis. RESULTS: By visual estimation, more than a 3-cm3 volume of CNS lymphoma was detected as an obvious focus of increased accumulation on delayed images. All other brain tumors tested appeared as decreased accumulation on delayed images. T/Ns and T/Cs on delayed images of CNS lymphomas, including tumors less than 3 cm3 in volume, were 1.48+/-0.42 and 1.08+/-0.16, respectively. These ratios in patients with glioma (0.30+/-0.05 and 0.31+/-0.07 respectively) or meningioma (0.34+/-0.10 and 0.41+/-0.17, respectively) showed a significant difference from those in patients with CNS lymphoma (P < 0.0005). CONCLUSION: 123I-IMP SPECT is a helpful tool for diagnosing CNS lymphoma.     

Quantitative measurement of regional cerebral blood flow with flow-sensitive alternating inversion recovery imaging: comparison with [iodine 123]-iodoamphetamin single photon emission CT

BACKGROUND AND PURPOSE: Flow-sensitive alternating inversion recovery (FAIR) MR imaging is a technique for depicting cerebral perfusion without contrast enhancement. Our purpose was to determine whether quantification at FAIR imaging can be used to assess regional cerebral blood flow (rCBF) in a manner similar to [iodine 123]-iodoamphetamin ((123)I-IMP) single photon emission CT (SPECT). METHODS: Nine patients with internal carotid or major cerebral arterial stenosis underwent (123)I-IMP SPECT and FAIR imaging (single section, different TIs, 1.5 T) at rest and after acetazolamide (Diamox) stress. FAIR and (123)I-IMP rCBF values were compared and correlated. Receiver operating characteristic analysis was conducted to detect hypoperfused segments on FAIR images. RESULTS: rCBF values of normally perfused segments were 41.53 and 51.91 mL/100 g/min for pre- and post-acetazolamide (123)I-IMP studies, respectively. Corresponding values for pre- and post-acetazolamide FAIR images, respectively, were 46.64 and 59.60 mL/100 g/min with a TI of 1200 milliseconds and 53.23 and 68.17 mL/100 g/min with a TI of 1400 milliseconds. (123)I-IMP and FAIR results were significantly correlated, with both pre- and post-acetazolamide images. Sensitivity (86%) in detecting hypoperfused segments was significantly higher with post-acetazolamide images (TI, 1400 milliseconds), and specificity (82-85%) and accuracy (80-82%) were higher with all pre- and post-acetazolamide images (all TIs). CONCLUSIONS: The significant correlation, high specificity and accuracy in detecting hypoperfused segments, similar increases in flow on both post-acetazolamide images, and absence of the need for contrast enhancement suggest that FAIR imaging, like nuclear medicine study, is complementary to routine MR imaging in the assessment of cerebral perfusion.     

"Luxury perfusion" with 99mTc-HMPAO and 123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of 123I-isopropyl-iodoamphetamine (123I-IMP) and 99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with 123I-IMP and 99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal 99mTc-HMPAO SPECT and abnormal 123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on 99mTc-HMPAO in areas corresponding to defects on the 123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination, 99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on 123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with 99mTc-HMPAO and was absent for both 123I-IMP and 99mTc-HMPAO in 3. We suggest that SPECT with 99mTc-HMPAO could show transient hyperemia not demonstrated by 123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with 99mTc-HMPAO than with 123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.     

Quantification of regional cerebral blood flow (rCBF) measurement with one point sampling by 123I-IMP SPECT]

A handy method of quantifying regional cerebral blood flow (rCBF) measurement by 123I-IMP SPECT was designed. A standard input function was made and the sampling time to calibrate this standard input function by one point sampling was optimized. An average standard input function was obtained from continuous arterial samplings of 12 healthy adults. The best sampling time was the minimum differential value between the integral calculus value of the standard input function calibrated by one point sampling and the input function by continuous arterial samplings. This time was 8 minutes after an intravenous injection of 123I-IMP and an error was estimated to be +/- 4.1%. The rCBF values by this method were evaluated by comparing them with the rCBF values of the input function with continuous arterial samplings in 2 healthy adults and a patient with cerebral infarction. A significant correlation (r = 0.764 (p less than 0.001)) was obtained between both.     

Single photon emission computed tomography (SPECT) using 99mTc-hexamethyl propyleneamine oxime in patients with ischemic cerebral diseases: comparative study of N-isopropyl-p-[123I]-iodoamphetamine and 99mTc-DTPA SPECT

In order to confirm the diagnosis and clarify the pathophysiology in the ischemic lesions in brain, 99mTc-PAO SPECT was performed in 42 patients with ischemic cerebral diseases, and the findings on 99mTc-PAO SPECT were compared with those on 123I-IMP or 99mTc-DTPA SPECT, and on X-CT. Furthermore, count ratio of ischemic lesion to normal contralateral region (I/N) was used for the evaluation of the detectability in the lesions on 99mTc-PAO or 123I-IMP SPECT, and less than 0.95 of I/N ratio was defined as the decreased accumulation. The detectability of ischemic lesion in brain with 99mTc-PAO SPECT was 80%, which was superior to that (60%) of LDA on X-CT. Especially, 99mTc-PAO SPECT was useful in cases which were examined early after the onset of the attack. On the other hand, 123I-IMP SPECT showed the best result (88%) in the detectability, and furthermore I/N ratio on 123I-IMP SPECT was lower than that on 99mTc-PAO SPECT. In the delayed phase on 123I-IMP SPECT the redistribution was observed in 30%, while on 99mTc-PAO SPECT it was done in none of them. The accumulation of 99mTc-DTPA in brain was found in 6 of 14 cases (43%), and 2 cases among them also showed the accumulation of 99mTc-PAO in the ischemic lesion. In such cases the destruction of BBB might be considered as the cause of the accumulation of 99mTc-PAO. Thus, 99mTc-PAO SPECT was thought to be useful method in clinical studies of the ischemic cerebral diseases.     

Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil.

1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia. METHODS: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-(14)C-octanoate and (123)I-IMP (or (123)I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4-7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were 0.8. RESULTS: 1-(14)C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-(14)C-octanoate were significantly higher than those for (123)I-IMP (4 h, 0.73 +/- 0.23 for 1-(14)C-octanoate and 0.37 +/- 0.20 for (123)I-IMP, P < 0.0001; 24 h, 0.84 +/- 0.11 for 1-(14)C-octanoate and 0.44 +/- 0.15 for (123)I-IMP, P < 0.0001) and those for (123)I-IMZ (4 h, 0.83 +/- 0.19 for 1-(14)C-octanoate and 0.57 +/- 0.13 for (123)I-IMZ, P < 0.0001; 24 h, 0.91 +/- 0.13 for 1-(14)C-octanoate and 0.73 +/- 0.06 for (123)I-IMZ, P < 0.0001). CONCLUSION: 1-(14)C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake. 1-(11)C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.     

Assessment of brain cell function using 123I-IMP SPECT of cerebral blood flow and visual evoked potential by photic stimulation in normal and demented elderly subjects]

Cerebral blood flow was quantitatively measured using 123I-IMP SPECT by photic stimulation and visual evoked potential (VEPs) in normal and dementia subjects: 8 with Alzheimer-type dementia, 9 with cerebrovascular dementia and 7 normal elderly subjects were divided into the three groups based on the Clinical Dementia Rating (CDR) grade: Group I (CDR 0), Group II (CDR 0.5-1), Group III (CDR 2-3). The 123I-IMP SPECT measurement was conducted at rest with the eyes closed and also during photic stimulation. VEPs were measured simultaneously. The results reveal prolongation of the P2 latency of the VEPs prolonged in accordance with the increasing severity of the dementia, and quantitative cerebral blood flow was lower in Group II and Group III than in Group I at rest, while during photic stimulation it significantly increased in Group I and II, but showed no change in Group III. The results suggest that quantitative measurement of cerebral blood flow using 123I-IMP SPECT by photic stimulation may enable more detailed assessment of brain cell function.     

Cerebral perfusion scintigraphy in patients with cerebrovascular disease by using 99mTc-ECD: comparative study with 123I-IMP SPECT

99mTc-ECD SPECT was performed in 19 patients with cerebrovascular disease, and location, extent, and severity of the lesions on 99mTc-ECD SPECT were compared with those on 123I-IMP SPECT. The initial brain uptake was 5.5 +/- 0.7% of the injected dose at 10 minutes after injection, 5.3 +/- 1.3% at 90 minutes, and clearance from the brain is slow. The distribution in the brain was changed, especially washout from the thalamus was slower than that from other regions. The count ratio of perfusion defect to normal area (D/N) on 99mTc-ECD SPECT was unchanged over the time, and had no significant differences from that on 123I-IMP SPECT. 99mTc-ECD SPECT was superior in detection of the lesion in the basal ganglia, and showed the images with superior spatial resolution due to physical characteristics of 99mTc. However, mild ischemic lesion and peri-infarct area was not clearly visualized, while 123I-IMP SPECT could demonstrate these lesions with better contrast.     

“Luxury perfusion” with99mTc-HMPAO and123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of¹²³I-isopropyl-iodoam-phetamine (¹²³I-IMP) and^99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with¹²³I-IMP and^99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal^99mTc-HMPAO SPECT and abnormal¹²³I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on^99mTc-HMPAO in areas corresponding to defects on the¹²³I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination,^99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on¹²³I-IMP. Crossed cerebellar diaschisis was found in 7 patients with^99mTc-HMPAO and was absent for both¹²³I-IMP and^99mTc-HMPAO in 3. We suggest that SPECT with⁹⁹mTc-HMPAO could show transient hyperemia not demonstrated by¹²³I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with^99mTc-HMPAO than with¹²³I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.     

Favorable biodistribution of99mTc-ECD for brain SPECT comparing with123I-IMP using alternative body scan

In order to evaluate the lung and brain uptake of 99mTc ethyl cysteinate dimer (99mTc-ECD) and N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP), alternative body scans were carried out in 15 cases of cerebrovascular disease. The biodistribution of 99mTc-ECD was 5.5 +/- 0.7%, 3.8 +/- 0.7% in the brain; 13.1 +/- 3.7%, 2.2 +/- 1.2%, in the lung at 15 min and at 4 hours, respectively, whereas that of 123I-IMP was 3.9 +/- 1.4%, 5.0 +/- 1.0% in the brain; 32.2 +/- 7.6%, 12.7 +/- 3.3%, in the lung at 15 min and at 4 hours, respectively. 99mTc-ECD accumulated in comparatively high amounts in the brain but remained low in the lung in the early image compared to 123I-IMP. However there was a high inverse correlation between brain and lung uptake of 123I-IMP (r = -0.82), but not of 99mTc-ECD (r = -0.18). We concluded that 99mTc-ECD had a better biodistribution in terms of low lung accumulation than 123I-IMP in brain SPECT.     

An assessment of the role of 123I-N-isopropyl-p-iodoamphetamine with single-photon emission computed tomography in the diagnosis of stroke and Alzheimer's disease

The role of 123I-N-isopropyl-p-iodoamphetamine (123I-IMP), a new agent used in brain imaging with single-photon emission computed tomography (SPECT), has been assessed in the early diagnosis of acute infarctive stroke and Alzheimer's disease (AD). The diagnosis of these conditions in their early stages has remained problematic, principally due to limitations of existing technologies. To more formally assess this new technology, we estimated the sensitivity and specificity of 123I-IMP SPECT scanning in the diagnosis of stroke and AD. We based our assessment on a review of all published studies that reported on 123I-IMP SPECT scans and which included three or more patients. The results from three major studies indicate that 123I-IMP SPECT scanning has a higher sensitivity (92% to 100%) than computerized tomography (55% to 86%) in the early diagnosis of acute cerebral infarction. Preliminary findings from studies using 123I-IMP SPECT in the diagnosis of early AD are promising and show a sensitivity of at least 69%. Furthermore, 123I-IMP SPECT scanning clearly discriminates patients with advanced AD from normals: sensitivity has ranged from 50% to 100%, while specificity has ranged from 97% to 100%. Studies also suggest that it can discriminate AD patients from those with multi-infarct dementia. Our review indicates that 123I-IMP SPECT may have an important future role in the early diagnosis and management of patients with acute infarctive stroke and AD.     

Evaluation of probable or possible dementia with lewy bodies using 123I-IMP brain perfusion SPECT, 123I-MIBG, and 99mTc-MIBI myocardial SPECT.

We evaluated the diagnostic usefulness of combination studies with a statistical mapping method in N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) brain perfusion SPECT, cardiac sympathetic nerve function by (123)I-metaiodobenzylguanidine ((123)I-MIBG), and myocardial function by electrocardiographically gated (99m)Tc-sestamibi ((99m)Tc-MIBI) SPECT for patients with probable or possible dementia with Lewy bodies (DLB). METHODS: Twelve patients with probable DLB (7 male, 5 female; mean age +/- SD, 72.3 +/- 5.63 y; range, 65-82 y) and 9 patients with possible DLB (3 male, 6 female; mean age +/- SD, 73.1 +/- 9.23 y; range, 59-88 y) were enrolled in this study. (123)I-IMP SPECT images were analyzed with 3-dimensional stereotactic surface projections (3D-SSP) and the severity of ischemia was classified objectively using quantitatively analytic and display software; stereotactic extraction estimation (SEE) methods were compared with a normal database. In addition, we evaluated (123)I-MIBG heart-to-mediastinum (H/M) uptake ratios. Moreover, we performed (99m)Tc-MIBI SPECT to evaluate myocardial perfusion and the left ventricular ejection fraction (LVEF) compared with a normal database. RESULTS: 3D-SSP images of group comparison with healthy control subjects showed significantly decreased perfusion in the parietotemporal, occipital cortex, posterior cingulated, and precuneus regions in the probable DLB group but no significant reduction in the possible DLB group. Mean H/M ratios in the probable DLB group were significantly lower than those of the possible DLB group and the control group, respectively. Ten of 12 patients (83.3%) with probable DLB and 1 of 9 patients (11.1%) with possible DLB showed severe reduction in the bilateral occipital lobe and also a low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 2 patients (22.2%) with possible DLB showed no bilateral occipital hypoperfusion but showed low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 6 patients (66.7%) with possible DLB showed no occipital hypoperfusion and normal (123)I-MIBG uptake. (99m)Tc-MIBI gated SPECT did not indicate any wall motion abnormality in any subjects. CONCLUSION: These results suggest that combined examination of cerebral blood flow with 3D-SSP and SEE analysis, and cardiac sympathetic nerve function with (123)I-MIBG, would be a useful supporting diagnostic method in patients with DLB-particularly, in possible DLB and when cerebral blood flow does not indicate occipital hypoperfusion.     

Estimation by static SPECT of the radioactivity remaining after the first dose of two-fractionated 123I-IMP administration: the rate of increase in cerebral blood flow by ARG and the rate of increase in SPECT count

We devised a method for estimating the radioactivity remaining after the first dose of two-fractionated tracer administration in the acetazolamide activation study in a facility where static SPECT is used for 123I-IMP cerebral blood flow scintigraphy. Three static SPECT scans were obtained over 9-min periods beginning 10 min after the first 123I-IMP administration, to estimate the remaining activity until after 60 min. In 72 patients at rest, 9-min SPECT was performed 6 times, and 11 different patterns of distribution and the fitting coefficient were obtained. The correlation between the actual measurement and the estimation at the mid scan time of 59.5 min could be expressed as y = 1.0064x - 1.9656, and r = 0.9972 (p < 0.01). The correlation between the first and second measurements of cerebral blood flow in 5 patients given two-fractionated administration at rest could be expressed as y = 0.9919x + 0.2978, r = 0.9976 (p < 0.01), indicating the usefulness of this method for estimating the radioactivity remaining after the first dose. In 57 patients with unilateral cerebrovascular disease, the cerebral blood flow on the unaffected side increased by 55.4 +/- 13.1%, whereas the blood flow in 19 regions exhibiting severe stenosis on the affected side was increased only 1.4 +/- 10.5% (p < 0.01). In addition, the correlation between the rate of increase in cerebral blood flow and the rate of increase in SPECT count could be expressed as y = 0.8415x + 0.291, and r = 0.9979 (p < 0.01). Thus, with this method, the cerebral hemodynamic reserve test using the rate of increase in cerebral blood flow by the ARG method or the rate of increase in SPECT count can be completed within a day while maintaining the image quality of static SPECT.     

Prediction of cerebral infarct sizes by cerebral blood flow SPECT performed in the early acute stage

Cerebral infarct due to embolic stroke without recanalization was examined by cerebral blood flow (CBF) SPECT in the early acute stage, and the possibility of predicting the size it will reach in the later stages was evaluated. Twenty patients (67 +/- 13 years) were examined by CBF SPECT with 99mTc-ECD 4.5 +/- 3.1 hours after the onset of cardiogenic cerebral embolism. The ratio of the anteroposterior length of the cerebral hemisphere to that of the severe ischemic region, which was defined as an area of clear-cut severe reduction in CBF as observed by SPECT, was calculated. One week after the onset, the cerebral infarct was measured in the same manner by CT, and the relationship between the two measurements was evaluated. The CBF in the region of severe ischemia and the surrounding region was determined by the Patlak plot method, and the affected/non-affected (A/NA) ratio was calculated. In severe ischemic regions the CBF ranged from 1.7 ml/100 g/min to 20 ml/100 g/min (mean, 11 +/- 5 ml/100 g/min), whereas the A/NA ratio ranged from 4% to 45% (mean, 26 +/- 11%). On the other hand, the CBF in the surrounding regions ranged from 20 ml/100 g/min to 52 ml/100 g/min (mean, 34 +/- 8 ml/100 g/min) whereas the A/NA ratio ranged from 52% to 104% (mean, 77 +/- 11%). The coefficient of correlation between the infarct size predicted by SPECT and that measured by CT was r = 0.986, and the correlation equation was Y = 1.047X - 2.969. CBF SPECT performed in the early acute stage can be used to predict the size of cerebral infarct.     

Preliminary study of patients with vertigo and dizziness using 123I-IMP

To study the application of cerebral blood flow scintigraphy with 123I-IMP for the evaluation of central dizziness, the difference in 123I-IMP accumulation between the right and left cerebellar hemispheres was determined as an asymmetry index (A.I.) in 8 normal subjects and compared with A.I. from patients with central dizziness. According to estimated lesions, 123I-IMP findings were compared with CT findings. The normal subjects had A.I. of 5.8 +/- 2.1%, whereas 36 patients with central dizziness had A.I. of 12.7 +/- 7.5%. On the basis of an A.I. of 8% or more as an abnormal finding on IMP scintigraphy, 11 of the 14 patients with estimated lesions of cerebellar hemispheres and 16 of the 20 with those of the whole cerebellum including the vermis were evaluated to have had abnormalities. Seven of 11 with estimated lesions of the brainstem and 4 of 5 with vertebrobasilar arterial insufficiency were evaluated to have had abnormalities. The findings of 123I-IMP cerebral blood flow scintigraphy were in good agreement with clinical symptoms in patients with central dizziness with estimated lesions of the cerebellar hemispheres, suggesting the possibility that this method is more useful than CT.