Iodine-123 iodoamphetamine brain scan in a patient with auditory hallucination

The case of an alcoholic patient with auditory hallucination is reported in which [123I] iodoamphetamine (IMP) brain imaging demonstrated increased accumulation in the left superior temporal lobe which corresponded to the left primary and secondary auditory areas. Thus, IMP brain scans seem to have the potential to objectively localize the brain abnormalities in auditory hallucination.     

Functional imaging of brain maturation in humans using iodine-123 iodoamphetamine and SPECT

The application of regional cerebral blood flow (rCBF) study by means of lipophilic radiotracers and single photon emission computed (SPECT) devices in very young infants is hampered by the considerable changes of rCBF pattern as a result of the cerebral maturation process. In an attempt to determine the normal evolution of [123I]IMP SPECT pattern as a function of age, we retrospectively selected the studies of 30 babies with normal clinical examination, EEG and CT or ultrasound scans at time of SPECT. There was a marked predominance of the thalamic perfusion over cortical areas until the end of the second month. The distribution of regional cortical activity followed a strict sequence. The perfusion of both parietal and occipital areas was well-visualized around the 40th week of gestational age and thereafter rapidly rose, always, however, with a slight predominance of the parietal activity. At the opposite, frontal activity which remained scarcely recognizable up to the second month tremendously rose to present the adult-like pattern at the beginning of the second year. The rCBF changes described above are well in agreement with the behavioral evolution occurring during prime infancy.     

Multispectral analysis of the temporal evolution of cerebral ischemia in the rat brain

A major difficulty in staging and predicting ischemic brain injury by magnetic resonance (MR) imaging is the time-varying nature of the MR parameters within the ischemic lesion. A new multispectral (MS) approach is described to characterize cerebral ischemia in a time-independent fashion. MS analysis of five MR parameters (mean diffusivity, diffusion anisotropy, T2, proton density, and perfusion) was employed to characterize the progression of ischemic lesion in the rat brain following 60 minutes of transient focal ischemia. k-Means (KM) and fuzzy c-means (FCM) classification methods were employed to define the acute and subacute ischemic lesion. KM produced an estimate of lesion volume that was highly correlated with postmortem infarct volume, independent of the age of the lesion. Overall classification rates for KM exceeded FCM at acute and subacute time points as follows: KM, 90.5%, 94.4%, and 95. 9%; FCM, 82.4%, 90.6%, and 82.6% (for 45 minutes, 180 minutes, and 24-120 hours post MCAO groups). MS analysis also offers a formal method of combining diffusion and perfusion parameters to provide an estimate of the ischemic penumbra (KM classification rate = 70.3%). J. Magn. Reson. Imaging 2000;12:842-858.     

Characteristics of the binding of N-isopropyl-p-[125I]iodoamphetamine in the rat brain synaptosomal membranes

N-isopropyl-p-[125I]iodoamphetamine (125I-IMP) binding to crude synaptosomal membranes of rat brain was saturable and pharmacologically displacable. Scatchard analysis of binding data revealed an apparent dissociation constant, KD of 56.2 +/- 5.2 microM, and the estimated maximum number of binding sites, Bmax of 7.5 +/- 1.1 nmoles mg-1 protein; and competition studies demonstrated structure activity relationships among structural analogues of arylalkylamines. These findings suggest that the retention mechanism of IMP in the brain is probably associated with saturable binding of IMP to extreme high-density, relatively low-affinity binding sites rather than any of the well-known amine receptors.     

Measurement of cerebral blood flow using graph plot analysis and I-123 iodoamphetamine

PURPOSE: N-isopropyl-p[I-123]iodoamphetamin (IMP) is transiently taken up by the lungs after intravenous injection and its concentration in arterial blood varies depending on the degree of I-123 IMP uptake and subsequent washout. A method that does not require arterial blood sampling would be valuable to measure cerebral blood flow (CBF) using I-123 IMP. METHODS: The authors developed a new theory and a convenient new method of CBF determination using I-123 IMP that does not require blood sampling. Dynamic images of the head and chest were acquired immediately after intravenous injection of I-123 IMP in a series of 42 consecutive patients with cerebrovascular disorders or other brain diseases (31 men, 11 women; mean age, 58 +/- 11 years). Changes in the I-123 IMP counts of the regions of interest set in the head and pulmonary trunk were analyzed by the graph plot method, and the F values (CBF index slope) determined were compared with the mean CBF levels obtained by simultaneous autoradiography. RESULT: The F values correlated well with the mean CBF obtained by autoradiography (r = 0.818, P < 0.001). CONCLUSIONS: This innovative I-123 IMP graph plot analysis method using the time-activity curve of the head and pulmonary trunk alone is a noninvasive, convenient way to measure CBF. It is expected to become the most useful clinical technique for measuring CBF with I-123 IMP. This method can be used for patient follow-up and for comparing different patient groups evaluated in regional CBF studies.     

Clinical usefulness of three-dimensional brain imaging with N-isopropyl-p-[123I]iodoamphetamine (IMP)

Three-dimensional reconstruction from N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography has been applied clinically to the detection of perfusion defects in 22 cases (15 cerebrovascular diseases and 7 normal controls confirmed by CT and MRI), with data being analyzed in terms of receiver operating characteristic curves (ROC). The results showed that three-dimensional (3-D) image could make better diagnostic capability especially in inexperienced examiner and that it was useful decreasing of difference of diagnostic capability. 3-D image could be taken within 1 minute and 15 seconds. We concluded that the three-dimensional brain imaging with IMP using this system was clinically useful because examiner could easily diagnose perfusion defects.     

Histochemical detection of ultrasmall superparamagnetic iron oxide (USPIO) contrast medium uptake in experimental brain ischemia.

Recently, macrophage infiltration in different central nervous system (CNS) pathologies has been visualized with ultrasmall particles of iron oxide (USPIO) as a new cell-specific contrast medium for MRI. However, validation of these findings at the histological level has been hampered by the fact that the in situ detection of iron uptake by conventional Prussian blue staining is not sensitive enough to detect low amounts of iron in the brain. Here, an improved method for the histochemical detection of USPIO uptake in ischemic brain lesions is reported. The procedure relies on the sequential enhancement of Prussian blue staining by diaminobenzidine and silver/gold impregnation. After photothrombotic cortical brain infarction, this method allowed sensitive in situ detection of iron-laden macrophages which matched both macrophage immunostaining and USPIO-induced signal alterations in high-resolution 7 T MRI. This staining method provides a basis for correlative histological assessment of USPIO-enhanced MRI in a broad spectrum of CNS pathologies.     

MR imaging of acute experimental ischemia in cats

The evolution of acute cerebral ischemia was documented by magnetic resonance (MR) imaging in 13 mongrel cats with occlusion of the middle cerebral artery through a transorbital approach. The animals were imaged under anesthesia at intervals from 30 min to 10 days after production of the lesion. An MR imager operating at 0.35 T was used with multislice, multi-spin-echo technique (TR = 500-2000 msec; TE = 28, 56 msec). The animals were sacrificed after imaging for pathologic correlation. Infarcts beyond 4 hr of age were visualized in all subjects. The earliest infarct was seen at 30 min (two cats) as an area of high signal intensity on T2-weighted images. In three other cats, however, 3-hr-old infarcts were not detectable. In one animal, a hemorrhage within a 1-week-old area of infarction was not characterized by MR imaging but was identified on CT scanning. The mass effect of the infarction appeared greatest at 2-4 days after infarction. The basal ganglia showed ischemic effects to best advantage. MR imaging offers previously unavailable sensitivity for the early noninvasive detection of cerebral ischemia in vivo.     

弥漫性脑损伤后脑缺血的实验研究

目的　运用大鼠弥漫性脑损伤 (DBI)模型研究脑外伤后脑缺血缺氧的形态学改变。　方法　采用Marmarou的DBI模型 ,光镜下观察微血管改变并测量顶叶皮质内微血管的截面积及微血管周的水肿面积 ;电镜下观察血脑屏障结构的形态学改变并半定量测定毛细血管周围的水肿范围。　结果　光镜下可见外伤后 2 ,6 ,2 4h微血管管径变窄 ,平均微血管截面积分别为 (41.77± 2 7.37) μm2 、(45 .0 9± 2 4 .75 ) μm2 、(49.38± 2 5 .13) μm2 ,均小于对照组 [(6 2 .0 7± 2 8.4 5 ) μm2 ](P <0 .0 5 )。伤后 6 ,2 4h微血管周围存在明显水肿。电镜下 2 ,6 ,2 4h血脑屏障结构有明显损害 ;微血管有痉挛、受压变窄及淤血三种改变。　结论　弥漫性脑损伤后存在明显的脑缺血缺氧的病理形态学改变。     

The relationship between N-isopropyl-p-[123I]iodoamphetamine accumulation in the brain and its dynamics in other organs

Single photon emission computed tomography of the brain and dynamic scintigraphy of the lung and liver with N-isopropyl-p-[123I]iodoamphetamine (IMP) were performed in 21 patients with and without cerebrovascular diseases to determine the relationship between IMP accumulation in the brain and its dynamics in other organs. The D/E ratios of the lung, liver and brain were calculated dividing the counts of the delayed image by that of the early image. The brain D/E ratio in the normal hemisphere was well correlated with the lung D/E ratio. So cases which showed more rapid lung washout tended to washout faster from the brain. We thought that this fact was affected by the systemic circulation. And the values of the brain D/E ratio of the cerebrovascular disease group were larger than that of the non-cerebrovascular disease group. This suggest the frequent existence of arteriosclerotic changes in patients of the cerebrovascular disease. Because the local brain washout was depended on the amount of the cerebral blood flow there. On the other hand, the lung D/E ratio was inversely correlated with the liver D/E ratio. In other words, more washout from the lung caused more accumulation of IMP in the liver. Also the brain D/E ratio was inversely correlated with the liver D/E ratio. In conclusion, there was a close relationship between IMP dynamics in the brain and that in other organs.     

MRI tissue characterization of experimental cerebral ischemia in rat

PURPOSE: To extend the ISODATA image segmentation method to characterize tissue damage in stroke, by generating an MRI score for each tissue that corresponds to its histological damage. MATERIALS AND METHODS: After preprocessing and segmentation (using ISODATA clustering), the proposed method scores tissue regions between 1 and 100. Score 1 is assigned to normal brain matter (white or gray matter), and score 100 to cerebrospinal fluid (CSF). Lesion zones are assigned a score based on their relative levels of similarities to normal brain matter and CSF. To evaluate the method, 15 rats were imaged by a 7T MRI system at one of three time points (acute, subacute, chronic) after MCA occlusion. Then they were killed and their brains were sliced and prepared for histological studies. MRI of two or three slices of each rat brain (using two DWI (b = 400, b = 800), one PDWI, one T2WI, and one T1WI) was performed, and an MRI score between 1 and 100 was determined for each region. Segmented regions were mapped onto the histology images and scored on a scale of 1-10 by an experienced pathologist. The MRI scores were validated by comparison with histology scores. To this end, correlation coefficients between the two scores (MRI and histology) were determined. RESULTS: Experimental results showed excellent correlations between MRI and histology scores at different time points. Depending on the reference tissue (gray matter or white matter) used in the standardization, the correlation coefficients ranged from 0.73 (P < 0.0001) to 0.78 (P < 0.0001) using the entire dataset, including acute, subacute, and chronic time points. This suggests that the proposed multiparametric approach accurately identified and characterized ischemic tissue in a rat model of cerebral ischemia at different stages of stroke evolution. CONCLUSION: The proposed approach scores tissue regions and characterizes them using unsupervised clustering and multiparametric image analysis techniques. The method can be used for a variety of applications in the field of computer-aided diagnosis and treatment, including evaluation of response to treatment. For example, volume changes for different zones of the lesion over time (e.g., tissue recovery) can be evaluated.     

Detection of malignant melanoma with iodine-123 iodoamphetamine

Iodoamphetamine (IMP) was shown by in vitro assay to have a high uptake by human melanotic melanoma cells, as compared to amelanotic melanoma cells. Eleven patients with proven malignant melanoma (MM) and 3 normal subjects were imaged at 2-4 hr and 16-24 hr after the i.v. injection 5 mCi (185 MBq) of [123I]IMP. One patient had a recurrent tumor that was subsequently shown to be squamous cell carcinoma. The index lesion was not visualized in the three patients with amelanotic melanomas. The index lesion/lesions were visualized in six of the seven other patients, except for 4/16 nodules in one patient. The seventh patient had a large, necrotic melanotic tumor that was not visualized, but an unsuspected lesion in the iliac nodes was detected. Multiple unsuspected lesions were detected in a second patient. While many lesions were seen at 2-4 hr, all lesions (other than a patient with small bowel disease) were seen best at 16-24 hr. No eye uptake was observed in any patient or control subject. Testicular uptake was seen in all males at 16-24 hr. Iodine-123 IMP appears to be a useful agent for the detection and follow-up of patients with melanotic MM.     

Diffusion as a mechanism of postmortem drug redistribution: An experimental study in rats

Summary In some cases of drug overdose there is a reservoir of unabsorbed drug in the stomach and gut. Furthermore, agonal aspiration might establish a second reservoir in the lungs. Two experimental rat models were used to study if diffusion from these reservoirs could contribute to the phenomenon of postmortem drug redistribution. Overnight fasted rats were sacrificed by CO₂ and 75 mg of amitriptyline (AMI) was administered by a gastric tube. In the first series (n = 19), the tubes were removed after AMI administration. In the second series (n = 17), the trachea was ligated and cut prior to drug administration to prevent airways contamination. The rats were left at room temperature on their back for a period of 5, 10, 24, 48, 96 up to 192 h and samples of heart blood, blood from the inferior vena cava, tissue samples from heart, lungs, different liver lobes, kidney and psoas muscle were taken. In both series of rats we observed that as early as 5 h postmortem increasing concentrations of amitriptyline were found in the liver lobes lying closest to the stomach. In rats where the trachea was not ligated, drug contamination of the lungs also resulted in an increase in drug concentration within 5 h in heart blood and heart muscle. In rats where the trachea had been ligated, amitriptyline was found in the lungs after 96 h postmortem. The main metabolite nortriptyline was also detected. We concluded that postmortem diffusion from the gastrointestinal tract could be a major mechanism behind the phenomenon of postmortem redistribution of drugs in human case material, and that agonal aspiration may be followed by a rapid increase in postmortem drug concentration in autopsy samples.