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In clinical practice, measurement of the rCBF has mainly been conducted by I-123-N-isopropyl-p-iodoamphetamine (123I-IMP) SPECT using the microsphere (MS) method, with continuous arterial blood sampling. While several non-invasive 123I-IMP quantification methods have been developed, their accuracy has been shown to be lower than that of the MS method. Therefore, a non-invasive quantification method for use in routine clinical practice is being sought. The purpose of this study was to develop a simple non-invasive 123I-IMP quantification method (SIMS method) with a simple input function-determining protocol based on the MS method. The input function for the SIMS method was determined using the administered dose and the integrated lung washout ratio obtained by analyzing the count–time activity curve of the pulmonary artery and lung on dynamic chest images. The mean CBF (mCBF) and input function measured in 80 patients by the SIMS method was compared with those determined using the MS method. A good correlation was observed between the counts measured by continuous arterial blood sampling in the MS method and the estimated counts by image analysis in the new method (r = 0.94, p

Cerebral vascular reserve (CVR) is an important indicator for the management of and therapy for cerebral arterial occlusive disease (CAOD). Vasodilatory function is measured using the standard IMP-ARG method. The IMP autoradiography (IMP-ARG) method employed here uses a standardized input function, which was derived from 12 patients between 31 and 71 years of age. Because the population of elderly patients continues to increase in Japan, additional therapies are required to assess CVR in elderly patients with chronic cardiopulmonary disease or a history of smoking, in particular. Despite its popularity, alternatives to the IMP-ARG method are necessary. Here, we proposed the microsphere (MS) method without an input function. Using this method and the IMP-ARG method, we measured the CVRs of 18 CAOD patients. The CVRs derived with these two methods were significantly and linearly correlated (r = 0.89, p

To semiquantify the uptake of N-isopropyl-p-[(123)I]-iodoamphetamine (I-123 IMP) in patients with uveal malignant melanoma reproducibly and objectively.Fifty-two patients were examined. Twenty-nine patients had malignant melanoma (group A), three were clinically diagnosed with metastatic choroidal tumor, and 20 patients were given either histological or clinical diagnoses of either benign pigmented lesion or tumor (group B). Early and delayed I-123 IMP images were obtained and standardized by Neurostat software. Using fusion software, we applied a three-dimensional region of interest (3D-ROI) template to the standardized I-123 IMP, and calculated the retention index and tumor-to-nontumor (T/N) ratio of the delayed phase using the maximum count for each ROI.Sensitivity at the retention index cutoff of 30 was 82.4%, specificity was 85.2%, and accuracy was 83.6%. Sensitivity at the T/N ratio of the delayed phase cutoff of 1.3 was 91.2%, specificity was 77.8%, and accuracy was 85.2%. The positive predictive value of the T/N ratio was better than that of the retention index. The negative predictive value of the retention index was better than that of the T/N ratio.This new semiquantitative estimation method is reproducible and objective, especially when the examinations are performed repeatedly for evaluation of both therapy and follow-up.

Single-photon emission computed tomography (SPECT) with iodine-123 (123I)-labeled N-isopropyl-p-iodoamphetamine (IMP) is widely used in measuring the cerebral blood flow (CBF) response to acetazolamide stress for assessment of cerebral vascular reserve. To quantitate CBF by means of SPECT with IMP, an autoradiographic (ARG) method has been developed and is widely used. Because the relation between the brain counts on the SPECT scan and CBF is not linear in the ARG method, a mixture of gray and white matter in a pixel causes errors in the calculation of CBF. In the present study, errors in the calculation of CBF and vascular response to acetazolamide stress by the ARG method due to tissue heterogeneity were estimated by simulation study. Correction for effects of tissue heterogeneity in SPECT data was also attempted.Images of gray and white matter fraction were obtained by voxel-based morphometry analysis of magnetic resonance (MR) imaging data set. Ideal CBF images, which were generated from gray and white matter fraction images with assumed blood flow values for gray and white matter, were compared to CBF images generated by the ARG method. Correction for effects of tissue heterogeneity in SPECT data was performed with gray and white matter fraction data obtained from MR images.Systematic underestimation of CBF due to tissue heterogeneity was observed in all brain regions. In the neocortical regions, underestimation by -21% to -16%, -26% to -20%, -31% to -24%, and -35% to -27% was observed for gray and white matter blood flow of 80 and 20, 100 and 25, 120 and 30, and 140 and 35 ml/100 ml/min, respectively. Vascular response was also systematically underestimated in most brain regions. Vascular responses in the neocortical regions ranged from 17% to 20%, from 31% to 37%, and from 42% to 52% when ideal vascular responses were 25%, 50%, and 75%, respectively. After correction for the effects of tissue heterogeneity, values of vascular response to acetazolamide stress ranged from 64% to 116% in the neocortical regions, whereas values obtained by the ARG method ranged from 48% to 52%.Underestimation of the vascular response to acetazolamide stress due to tissue heterogeneity should be considered in the estimation of cerebral vascular reserve.

Objectives: Iodine-123 (123I)-labeledN-isopropyl-p-iodoamphetamine (IMP) has been used as a cerebral blood flow (CBF) tracer for single-photon emission computed tomography (SPECT), and measurements of the CBF response to acetazolamide stress by SPECT with IMP are widely used to assess cerebral vascular reserve. To quantitate CBF by means of SPECT with IMP, an autoradiographic (ARG) method has been developed and is widely used. In the ARG method, CBF is calculated from the brain counts of the SPECT scan with an assumed distribution volume value of IMP (Vd). However, differences between true Vd and assumed Vd results in errors in calculated CBF. In the present study, errors in the CBF response to acetazolamide stress as calculated by the ARG method were investigated.Methods: SPECT studies were performed on 12 patients with steno-occlusive lesions of the major cerebral artery. Two studies were performed on separate days. The first study was performed at rest (baseline), and the second during acetazolamide stress. SPECT scans were performed at 40 min (early scan) and 180 min (delayed scan) after intravenous injection of IMP.Results: Although a simulation study showed that errors in calculated changes in CBF in response to acetazolamide stress, which result from differences between the true Vd and the assumed Vd, were larger when the baseline CBF and change in CBF were larger, values calculated by the ARG method with an assumed Vd were in good agreement with those calculated with true Vd obtained from early and delayed scan data.Conclusion: These data indicate that errors in the calculated CBF response to acetazolamide stress as calculated by the ARG method are negligible even at high CBF responses. The ARG method is therefore reliable for measurement of CBF response to acetazolamide stress.

However, extracranial and intracranial arterial bypass surgery (EC/IC BYPASS) was denied by the randomized study, some patients may be suitable for surgery after selecting areas of misery perfusion. Steady-state O-15 positron emission tomography (PET) showed cerebral blood flow of 31.6±4.1 (ml/100 g/min) with acetazolamide reactivity of 30.6±5.4 (%) in misery perfused areas. The authors examined whether or not patients could be selected for surgery through combining cerebral blood flow (CBF) measurements with vasoreactivity determined by I-123 IMP (IMP; N-isopropyl-p-[I-123]-iodoamphetamine) single-photon emission-computed tomography (SPECT), which has good linearization at high flow ranges. Cerebral blood flow was quantified immediately after PET in 24 patients by counting I-123 IMP in arterial blood 10 min after injection. The CBF in the middle-cerebral arterial territories (MCA) was obtained by selecting regions of interest and comparing the fit between O-15 H2O and I-123 IMP using a nonlinear PS model curve. In 48 MCA areas, the CBF correlation between brain PET and IMP brain SPECT was close according to the equation, PET=12.4+0.46×IMP; r=0.743 (p

Ga-67 citrate scintigraphy in the management of malignant lymphomas is well established. It cannot, however, differentiate malignant from benign lesions because this agent also accumulates in benign inflammatory lesions. The authors present a case of increased I-123 IMP uptake on both early and delayed SPECT images in a patient with malignant lymphoma of the central nervous system. Results show that I-123 IMP SPECT can help differentiate malignant lymphoma from benign lesions and other malignant brain tumors.

The transmission dependent convolution subtraction method which is one of the methods for scatter correction of SPECT was applied to the assessment of CBF using SPECT and I-123-IMP. The effects of scatter correction on regional distribution of CBF were evaluated on a pixel by pixel basis by means of an anatomic standardization technique. SPECT scan was performed on six healthy men. Image reconstruction was carried out with and without the scatter correction. All reconstructed images were globally normalized for the radioactivity of each pixel, and transformed into a standard brain anatomy. After anatomic standardization, the average SPECT images were calculated for scatter corrected and uncorrected groups, and these groups were compared on pixel by pixel basis. In the scatter uncorrected group, a significant overestimation of CBF was observed in the deep cerebral white matter, pons, thalamus, putamen, hippocampal region and cingulate gyrus as compared with scatter corrected group. A significant underestimation was observed in all neocortical regions, especially in the occipital and parietal lobes, and the cerebellar cortex. The regional distribution of CBF obtained by scatter corrected SPECT was similar to that obtained by O-15 water PET. The scatter correction is needed for the assessment of CBF using SPECT.

Experimentally we investigated the detection of lung cancer with N-isopropyl-p-I-123-iodoamphetamine (I-123 IMP). Various tumors including Lewis lung cancer were used as tumor models. Serial images were obtained. Biodistribution of Lewis lung cancer was performed. In Lewis lung cancer good visualization as in B-16 melanoma and high tumor accumulation were found with IMP. In conclusion, due to its greater accumulation almost equivalent to that in melanotic melanoma, I-123 IMP may have a role in the detection of lung cancer.

To evaluate the redistribution phenomenon on delayed 1-123 IMP SPECT images of children and adolescents with partial seizures, 25 patients were selected and investigated in the interictal state. Early and delayed SPECT were performed 15-20 minutes and 5 hours, respectively, after 1-123 IMP injection. Redistribution patterns were classified into three groups : 1) redistribution (RD) (-) group (n = 5), in which a low-uptake area on the early image persisted or was enlarged on the delayed image, 2) RD (+) group (n = 14), in which a low-uptake area on the early image changed to normal distribution on the delayed image, and 3) marked redistribution (MRD) (+) group (n = 6), in which a low-uptake area on the early image changed to a high uptake area on the delayed image. Among the patients who were followed for at least 12 months after the SPECT scans, the short-term clinical outcome tended to be good in the RD (+) group, intermediate in the MRD (+) group, and poor in the RD (-) group. These results of our preliminary comparative study indicate that the redistribution pattern of 1-123 IMP may be related to the clinical aspects in patients with partial seizures and that it may play an important role in predicting their short-term clinical outcome.

123I-IMP lung scintigraphy was performed in two patients with primary malignant lymphoma, whose radiographic features were difficult to differentiate from inflammatory or atelectatic lesions. 123I-IMP scans revealed a defect in the lesions on the delayed (24 hr) image, suggesting a tumorous lesion. 123I-IMP scan may contribute to differential diagnosis of this rare tumorous entity from benign disorders having a different appearance.

We report the case of a 25-year-old woman with systemic lupus erythematosus. She complained of headache and left hemiparesis and was admitted to our hospital. She was in a coma after admission. Brain MRI showed no abnormalities, but brain single photon emission computed tomography showed diffuse hyperperfusion in the right frontal and temporal lobes. The calculated measured regional cerebral blood flow in the right hemisphere was increased to 40 to 55 mL/100 g/min, and that in the left was within the normal range of 25 to 35 mL/100 g/min. Two months later, the hyperperfusion was disappeared. The hyperperfusion could be explained by inflammatory changes.

Quantitative measurements of regional cerebral blood flow with N-isopropyl-(Iodine 123)p-iodoamphetamine (I-123 IMP) as a microsphere model were performed in forty cases. The regional cerebral blood flow values obtained with I-123 IMP were slightly underestimated compared with those of Xe-133 inhalation methods (y = 0.90x-2.1, r = 0.85, p less than 0.01). After correction by global extraction (87%) between the artery and internal jugular vein, which was measured in four patients by means of a catheter technique, the underestimation of the values obtained with I-123 IMP was improved (y = 1.0x-2.4, r = 0.85, p less than 0.01). Several problems in the accurate quantitative measurement of regional cerebral blood flow with I-123 IMP are discussed.

Forty-six epileptic patients with partial seizures and normal CT underwent 48 examinations of early and delayed SPECT using I-123 IMP in the interictal phase. One of them underwent a follow-up SPECT in a more stable state compared to the first SPECT. Another patient, with informed consent, underwent a follow-up SPECT in combination with pharmacologic activation with bemegride. Early SPECT was performed 30 minutes after an IMP injection and delayed SPECT 4 to 4 1/2 hours later. Temporal changes in uptake pattern were visually classified into six types and compared with known patterns of SPECT uptake in relation to ischemic, hyperemic, and other changes. These were also correlated with the amount of epileptic activity seen on the EEG.

I-123 IMP scintigraphy was performed on a 59-year-old man with malignant melanoma. The images showed diffuse uptake in the bone marrow. These findings were more evident when using I-123 IMP than with Ga-67 citrate. I-123 IMP does not normally concentrate in the bone marrow. I-123 IMP scintigraphy may be more sensitive and specific in evaluating the bone marrow metastases from a malignant melanoma.

I-123 iodoamphetamine (IMP) and Ga-67 scintigraphy of malignant melanoma were performed to compare the accumulation of these tracers regarding tumor diameter to determine the site of I-123 IMP accumulation and to evaluate the use of I-123 IMP and Ga-67 in postoperative follow-up. The studies involved 44 patients with a definite diagnosis of malignant melanoma during a 10-year period from April 1991 through March 2001. In this study a very high detection rate of 90.9% was obtained for primary foci with 1-123 IMP. With Ga-67, the primary site detection rate was 25%. The results suggest that 1-123 IMP is superior to Ga-67 with respect to the detection rate of primary site.

Nine subjects with late onset unipolar depression were studied, before and after treatment, using I-123 iodoamphetamine SPECT. In all nine subjects clinical improvement was associated with a significant increase (p

Radiation angiopathy was developed by the process of accelerated atherosclerosis at the site of irradiation. The case of a 44-year-old man with right hemiparesis showing a high signal intensity in the left semioval center on MRI and a defect in the left temporo-parietal area with subsequent filling-in with I-123 IMP brain SPECT is reported. Digital subtraction angiography showed typical radiation angiopathy with ulceration in the left common carotid artery. Twenty-four years previously, he underwent curative irradiation of a neck mass that revealed Hodgkin's disease by biopsy. The emboli formed at the site of radiation-induced angiopathy and caused cerebral infarction. The perfusion abnormality in the territory of the embolic artery was detected by I-123 IMP SPECT. Long-term survivors of neck irradiation are at high risk for the development of carotid arterial disease and should be watched carefully.

A total of 24 patients with a mean age of 45.8 +/- 20.8 were included in the study. The patients were grouped as Control (C), Degenerative Syndromes (DS), Degeneration Associated with External Factors (DEF), Degeneration Associated with Focal Neurologic Lesion (DFN) and Demyelinating Disease (DM). Imaging started 15 minutes for early and 4 hours for delayed scans after i.v. infusion of I-123 IMP. The rCBF was calculated by the IMP autoradiographic (ARG) method. The wash-out ratio (WR) was calculated as the ratio of the Delay/Early count. In the rCBF of the various areas of the brain, significant differences were noted between various disease groups. No correlation was noted between rCBF and WR (r = -0.50). The WR of patients grouped according to various disease processes did not show a significant difference between various areas of the brain. In conclusion, the rCBF was effective in separating both various areas of the brain and disease entities. WR from a delayed study is less useful in neurodegenerative diseases.

Although Tc-99m HMPAO uptakes in various brain tumors have been reported, SPECT images of neurocytoma have not been described. The authors report a patient with intraventricular neurocytoma (IN) who demonstrated significant uptake of Tc-99m HMPAO and Tl-201 Cl before brain biopsy. Residual tumor after biopsy showed significant uptake of I-123 IMP on early SPECT images, but this uptake was decreased on delayed images. The three radionuclides seem to have different uptake mechanisms.

1-123 IMP is now widely used as a radioactive agent for cerebral blood flow scintigraphy. It is also known to accumulate in certain types of tumors. The authors present a case in which 1-123 IMP accumulated in peritoneal metastases of hepatocellular carcinoma.

In pulmonary disease, the clearance of N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) from the lung is prolonged, and retention of the tracer is noted in the pulmonary lesion as a result of damage to the pulmonary endothelium. A patient with acute pulmonary thromboembolism was examined using I-123 IMP pulmonary SPECT. The patient was treated with heparin after the early images were obtained but before the delayed images. The early images showed mildly reduced distribution of the tracer in the right lower lobe. Delayed images showed no retantion of the tracer. The findings indicate that pulmonary endothelial cells in a transient, pulmonary arterial hypoperfused area may remain intact.

N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT studies were performed on a 75-year-old patient who could be clinically classified as subcortical arteriosclerotic encephalopathy (Binswanger's disease). Regional cerebral blood flow (rCBF) was quantitatively measured by a microsphere model, and was diffusely decreased in the whole brain (mean rCBF: 36 ml/100 g/minute). After a ventriculoperitoneal shunt operation, his clinical symptoms were markedly improved, and the improvement was validated by a 32% increase of mean rCBF. However, MRI and CT images showed no significant interval changes before and after the shunt operation. Regional rCBF measurement by I-123 IMP SPECT should be performed and plays an important role in the evaluation of Binswanger's disease.

MR images and three dimensional surface images (3-D images) using N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) were obtained in a patient who acknowledged using thinner and amphetamine. While MR images could not find any definite abnormality, 3-D images with I-123 IMP demonstrated multifocal defects. 3-D images with I-123 IMP might be able to detect an early abnormality in brain perfusion in a drug abuser.

We compared I-123 IMP and 99m-Tc HMPAO SPECT studies with 0–15 H2O and F-18 FDG PET studies, and evaluated the clinical significance of SPECT studies in dementia. Seventeen patients including 9 patients with Alzheimer’s disease, 3 patients with Pick’s disease and 5 patients with multi-infarct dementia were studied. IMP and HMPAO SPECT studies could not detect mildly affected areas when compared with FDG PET. However, they revealed decreased perfusion in the bilateral parietal regions in Alzheimer’s disease and in the bilateral frontal regions in Pick’s disease, while MRI and/or CT showed mild to moderate cerebral atrophy. IMP and HMPAO SPECT studies can be easily performed in clinical practice, and these findings were useful in the differential diagnosis of dementia. Our preliminary results suggested that SPECT studies with I-123 IMP and Tc-99m HMPAO, despite their limitations, are useful in the differential diagnosis of dementia.

I-123 IMP is now widely used as a radioactive material for cerebral blood flow scintigraphy. It is also known that this substance will accumulate in certain types of tumors. The authors present a case of a 47-year-old woman who showed accumulation of I-123 IMP in hepatic cell adenoma. 6 refs., 3 figs.

A 52-year-old woman with normal mentation experienced slowly progressive muscle weakness an atrophy in lower limbs for seven months. She was diagnosed as amyotrophic lateral sclerosis with upper and lower motor neuron signs by neurological examination, EMG and muscle biopsy from the right biceps brachii muscle. Brain CT and MRI showed no adnormal densities. Three-Brain CT and MRI showed no abnormal densities

A 63-year-old woman with numbness of the fingers bilaterally underwent I-123 IMP SPECT and magnetic resonance imaging. On both early and delayed SPECT images with I-123 IMP, increased accumulation of I-123 IMP was noted in the posterior horn of the left lateral ventricle and in the white matter of the left parieto-occipital lobe. These areas were consistent with lesions of which the signal intensity approximates that of the normal gray matter on all pulse sequences. Thus, a focally increased accumulation in the white matter on both early and delayed SPECT images with I-123 IMP may reflect heterotopic gray matter

We performed I-123-IMP SPECT brain imaging on seven mildly demented AIDS patients and seven normal subjects. In an attempt to detect and quantitate regions of decreased I-123-IMP uptake, pixel intensity histograms of normalized SPECT images at the basal ganglia level were analyzed for the fraction of pixels in the lowest quartile of the intensity range. This fraction (F) averaged 17.5% (S.D. = 4.6) in the AIDS group and 12.6% (S.D. = 5.1) in the normal group (p less than .05). Six of the AIDS patients underwent neuropsychological testing (NPT). NPT showed the patients to have a variety of mild abnormalities. Regression analysis of NPT scores versus F yielded a correlation coefficient of .80 (p less than .05). We conclude that analysis of I-123-IMP SPECT image pixel intensity distribution is potentially sensitive in detecting abnormalities associated with AIDS dementia and may correlate with the severity of dementia as measured by NPT.

Using N-isopropyl-(I-123)p-iodo-amphetamine (I-123 IMP) and gallium-67 citrate, it was possible to detect human malignant melanomas. I-123 IMP imaging was helpful in detecting melanomas occurring in the legs and arms, and the 4 hour image was better than the 1 hour image. Moreover, while gallium scintigraphy more clearly detects human malignant melanoma, I-123 IMP allows for the detection of human malignant melanoma within 1 hour after administration.

Ten patients with unusual uptake and retention of I-123 IMP in their brain tumors were studied. Of these ten patients, five had meningiomas and the remaining five had glioblastoma, malignant astrocytoma, malignant lymphoma, metastatic brain tumor, and cellular blue nevus. Six tumors (five meningiomas and the glioblastoma) showed short term retention of I-123 IMP. Three tumors (the malignant astrocytoma, the malignant lymphoma, and the metastatic brain tumor) showed a delayed increase of radioactivity and the cellular blue nevus showed a gradual increase and long term retention of the tracer.

We evaluated the significance of redistribution in 123I-IMP SPECT study using PET. Twelve lesions in ten patients were selected. These lesions were classified into the following three groups; ischemia, infarction of subacute phase and infarction of chronic phase. All lesions with ischemia or subacute infarction showed good or moderate redistribution. Three of four lesions with chronic infarction showed no redistribution. The mean values of rCBF and rCMRO2 were highest in the lesions with good redistribution, but there was no differences in rOEF with the degree of redistribution. In conclusion, the tissue with good redistribution is not always viable and it was impossible to predict a region with increased rOEF by redistribution alone.