Clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.

BACKGROUND: No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination. OBJECTIVE: To identify a reliable marker for the clinical diagnosis of MM2-type sCJD. METHODS: CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses. RESULTS: The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on [18F]2-fluoro-2-deoxy-d-glucose PET. CONCLUSION: For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or [18F]2-fluoro-2-deoxy-d-glucose PET for the thalamic form.

Effect of vagal autotransplantation on quantitative [3H]-vesamicol binding image in rats with unilateral lesions of nucleus baslis magnocellularis.

It is considered that nodosal ganglion grafting improves learning and memory disorder in nucleus basalis magnocellularis lesioned rats, and that [3H]-vesamicol is one of the mapping agents for presynaptic cholinergic neurons. Quantitative autoradiography was performed using high sensitive imaging plate system to evaluate the effect of neurotransplantation on [3H]-vesamicol binding. The affected-side to unaffected-side ratio of [3H]-vesamicol in the nucleus basalis magnocellularis lesioned group was significantly lower than that in the sham-operated group at 1, 2 and 4weeks (P<0.01). In the transplanted group, the ratio was significantly higher than that in the untreated group at 4weeks (P<0.05). [3H]-vesamicol binding is one of the most sensitive indicators of nucleus basalis magnocellularis lesions and the effect of the nodosal ganglion grafting.

Reduction of vesicular acetylcholine transporter in beta-amyloid protein-infused rats with memory impairment.

The aim of this study was to investigate spatial memory and quantitative acetylcholine transporter autoradiography using a high-sensitivity imaging plate system in rats treated with beta-amyloid protein, a model of Alzheimer's disease. An eight-arm radial maze was used to evaluate spatial memory. The performance of the eight-arm radial maze task was impaired in beta-amyloid protein-treated rats. In the parietal cortex, [3H]-vesamicol binding to the vesicular acetylcholine transporter was significantly lower in beta-amyloid protein-treated rats than in vehicle-treated rats, and was significantly correlated with the mean number of correct selections in the maze task of the first 5 days in the post-operative state. These results indicate that the reduction in [3H]-vesamicol binding to vesicular acetylcholine transporter is related to memory impairment induced by beta-amyloid protein. Beta-amyloid protein-infused rats with spatial memory impairment may be useful for the development of new radiolabelled vesamicol analogues for the objective evaluation of Alzheimer's disease.

[Quantitative evaluation for scatter and attenuation correction in 99mTc SPECT--multicenter cooperation phantom study].

A multicenter cooperation phantom study was conducted to evaluate the accuracy of a triple energy window scatter correction technique in combination with various attenuation correction methods for 99mTc single photon emission computed tomography (SPECT) imaging. Six centers participated in this research and the data obtained with seven SPECT instruments were analyzed. The phantom used in the experiment was a 20 x 10 cm cylinder filled with homogeneous 99mTc solution, containing two kinds of cold spots (cold rod phantoms). One had a water-filled cylinder 5.5 cm in diameter positioned 2.5 cm from the center. The other contained 6 water-filled cylinders of various sizes. Contrasts of cold regions were in the range from 74% to 120% (true 100%). Another phantom had the shape of a pie-chart divided into six chambers symmetrically positioned in a cylinder 20 cm in diameter and 10 cm in height. Each chamber had volume of 480 ml and contained homogeneous 99mTc solution of different concentrations. This phantom was used to test for linearity between the radio activity concentration and reconstructed count density (linearity phantom). The intercept of the regression line obtained from the linearity phantom was 8.4 kBq ml-1 without scatter correction and -6.8 kBq ml-1 with scatter correction. Contrast was in the range from 78% to 132% (true 100%). The mean relative error for the measured activity concentration was 4.9% +/- 3.5% (mean +/- sd).

Age-related changes in the cerebral distribution of 99mTc-ECD from infancy to adulthood.

UNLABELLED: Although cerebral blood flow in infants differs from that in older individuals, the distribution of 99mTc-ethyl cysteinate dimer (ECD) in infants has not been well studied. This study compared 99mTc-ECD distribution in infants and children with that in young adults. METHODS: 99mTc-ECD SPECT was performed on 37 patients suspected of having epilepsy, ranging in age from 3 mo to 26 y. The patients were divided into two age-matched groups, a drug-free group (n = 19) and a drug-taking group (n = 18), according to their anticonvulsant medication status at the time of examination. 99mTc-ECD (100-740 MBq) was injected interictally, and SPECT data were acquired using a triple-head gamma camera. Mean whole-brain counts were obtained from 10 sequential SPECT images. Regions of interest were set bilaterally on five areas of the cerebral cortex and on the basal ganglia, thalamus and cerebellum. The brain perfusion index (BPI) was obtained as a ratio of the mean counts in each region of interest to the mean whole-brain counts. The relationship between BPI and age in each region in the drug-free and drug-taking groups was analyzed separately and together using linear regression. The relationship between five patient age groups (<1 y, n = 4; 1-4 y, n = 9; 5-9 y, n = 8; 10-15 y, n = 7; >15 y, n = 9) and BPI in each region was also examined using multiple comparison analyses. RESULTS: Significant positive correlations between BPI and age in the frontal cortex and cerebellum were confirmed in the drug-free group. Anticonvulsant drugs did not affect the regression lines of BPI in the frontal cortex and cerebellum. Significant differences in BPI between age groups were seen in the parietal cortex, frontal cortex, occipital cortex, basal ganglia, thalamus and cerebellum in all patients. CONCLUSION: Age-related changes in cerebral 99mTc-ECD distribution were confirmed and found to be unaffected by the administration of anticonvulsant drugs. 99mTc-ECD uptake in children and infants is different from cerebral blood flow glucose metabolism as previously reported, especially in the cerebellum.

Asymmetries of benzodiazepine receptor binding potential in the inferior medial temporal lobe and cerebellum detected with 123I-iomazenil SPECT in comparison with 99mTc-HMPAO SPECT in patients with partial epilepsy.

We examined the relation between regional 123I-iomazenil (IMZ) parameters and cerebral blood flow (CBF) to evaluate the difference between the quantitative parameters of IMZ and the CBF in detecting epileptic abnormality. Seventeen patients with unilateral partial epilepsy were subjected to 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT, and early and delayed IMZ SPECT. Then we quantitatively obtained the blood-to-brain transfer constants (K1) and binding potentials (BP) for nine regions of interest, and the regional CBF was also by using the simple angiographic method. From our data, significant asymmetries of BP in the inferior medial temporal lobe and cerebellum were shown and may be related to a remote effect such as crossed cerebellar diaschisis. In conclusion, the asymmetry of BP with iomazenil SPECT was demonstrated in patients with unilateral epilepsy that was not detectable by HMPAO SPECT.

Discrepancy between blood flow and muscarinic receptor distribution in rat brain after middle cerebral artery occlusion.

To clarify whether muscarinic acetylcholine receptor (mAChR) binding can be a viable muscarinic neuronal marker which provides therapeutic information different from perfusional information in global brain, we evaluated the discrepancy between the distribution of cerebral blood flow (CBF), mAChR and its five subtypes of messenger ribonucleic acid (mRNA) in the acute (n=9) and chronic (n=8) phases of a middle cerebral artery (MCA) occlusion model and in sham-operated controls (n=6). In the acute phase, regional CBF was markedly reduced in the MCA territory, whereas mAChR was not reduced and the mRNA was reduced only slightly. In the chronic phase, mAChR was reduced markedly in the infarcted lesion and the mRNA was also reduced. The mAChR was slightly reduced in the ipsilateral substantia nigra and pontine nucleus because of remote effects; however, regional CBF in the substantia nigra was slightly increased and did not change in the pontine nucleus. The discrepancy between CBF and mAChR was clarified, and the tendency toward a reduction in mRNA in the acute ischaemic region without a reduction in mAChR suggested the presence of cholinergic neurons which were viable but hypometabolic. It is concluded that mAChR imaging may be of value for the assessment of the viable cholinergic neuron density in vivo.

Intense Ga-67 uptake in adenosquamous carcinoma of the pancreas.

Gallium-67 citrate (Ga-67) scintigraphy was performed in a patient with adenosquamous carcinoma of the pancreas. Intense and homogeneous uptake was observed in the tumor. Few reports have dealt with Ga-67 findings in pancreatic cancers. Ga-67 uptake in the tumor was assumed to be due to accumulation in the component of squamous cell carcinoma. This case suggested that Ga-67 citrate scintigraphy may be useful in detecting adenosquamous carcinoma of the pancreas. To our knowledge, no report has described findings of Ga-67 citrate scintigraphy of adenosquamous carcinoma of the pancreas. Radiologists should remember adenosquamous carcinoma of the pancreas when encountering such scintigraphic findings.

Dual-tracer autoradiography using 125I-iomazenil and 99Tcm-HMPAO in experimental brain ischaemia.

To investigate the utility of neuroreceptor imaging in ischaemic cerebrovascular disorders, dual-tracer autoradiography using 99Tcm-hexamethylpropyleneamine oxime (HMPAO) for the evaluation of cerebral blood flow and 125I-iomazenil for the evaluation of central-type benzodiazepine receptor density was performed in experimental brain ischaemia created by occlusion of the unilateral middle cerebral artery of the rat. In the acute phase of ischaemia, 125I-iomazenil accumulation showed less of a decrease than 99Tcm-HMPAO in the cerebral cortex of the lateral convexity and in the lateral segment of the caudate putamen in the lesioned cerebral hemisphere. In the sub-acute phase, both 125I-iomazenil and 99Tcm-HMPAO accumulation increased in the lesion compared with the acute phase. A large accumulation of 99Tcm-HMPAO and 125I-iomazenil in the lesion was considered to be due to luxury perfusion and penetration of 125I-iomazenil hydrophilic metabolites from the blood into the brain tissue through the altered blood-brain barrier. In the chronic phase, 125I-iomazenil accumulation showed a more marked decrease than 99Tcm-HMPAO in the lesion. Moreover, the ipsilateral thalamus, which is remote from the lesion, revealed decreased 125I-iomazenil accumulation despite normal 99Tcm-HMPAO accumulation. Since the central-type benzodiazepine receptors are principally located not on the glial cells but on the neurons, the receptor density may exhibit a change that parallels the neuron density. These results suggest that central-type benzodiazepine receptor imaging is useful for the evaluation of neuronal damage when used in conjunction with brain perfusion imaging in ischaemic cerebrovascular disorders, except in the sub-acute phase.

Synthesis of radioiodinated analogs of 2-(4-phenylpiperidino)cyclohexanol (vesamicol) as vesamicol-like agent.

Three iodovesamicol analogs, iodinated at the ortho, meta, and para positions of the 4-phenylpiperidine moiety, were synthesized and labeled with 125I by isotopic exchange reaction. Their potencies as a vesamicol-like drug were evaluated with competitive inhibition studies using (-)[3H]vesamicol. The radiochemical yields were 40-85%, the radiochemical purities exceeded 95% and their specific activities were 370-740 GBq/mmol. The descending order of binding affinity of the tested compounds against the vesamicol receptor was m-iodovesamicol > o-iodovesamicol > p-iodovesamicol. The receptor binding affinity of m-iodovesamicol (IC50 = 133 nM) was comparable with that of vesamicol (IC50 = 109 nM). Therefore, the meta position of the 4-phenylpiperidinyl fragment of vesamicol was the optimum site for iodination, and radioiodinated m-iodovesamicol may serve as a useful radiopharmaceutical for in vitro and in vivo studies of presynaptic cholinergic neurons in rats.

Regional uptake of iodine-125-metaiodobenzylguanidine in the rat heart.

Regional uptake of iodine-125-metaiodobenzylguanidine ([125I]MIBG) was evaluated in normal (n = 12) and reserpinized (n = 12) rat hearts. At 15 min and 1, 3 and 6 h after injection of [125I]MIBG, tissue activities were calculated for the right ventricular myocardium (RV), the whole left ventricular myocardium (whole LV), the epicardial layer of the left ventricular myocardium (Ep LV), the endocardial layer of the left ventricular myocardium (En LV), the basal segment of the left ventricular myocardium and the apical segment of the left ventricular myocardium. The uptake of [125I]MIBG at 6 h after injection in the normal rat heart was higher in RV than in whole LV (0.45 +/- 0.09% vs 0.30 +/- 0.06% kg dose/g), and in Ep LV than in En LV (0.32 +/- 0.07% vs 0.25 +/- 0.05%). In the reserpinized rat heart, the difference in the uptake between Ep LV and En LV was smaller. This suggests that the difference in the regional [125I]MIBG uptake might reflect different intravesicular uptake in the layers of the heart. To our knowledge, the low uptake in the endocardial layer was a new finding which seems to indicate a difference in innervation between the epicardial and endocardial layers of the left ventricle in the rat heart. Autoradiographic study also showed the low uptake of [125I]MIBG in the endocardial layer, while homogeneous perfusion was observed with thallium-201, supporting the tissue uptake study. Thus, the endocardial and epicardial layers of the left ventricle in the rat heart were considered to be differently innervated.

[Central type benzodiazepine receptor and cerebral blood flow in experimental chronic brain infarction--evaluation using a double-tracer autoradiography technique].

Double tracer autoradiography was performed to measure regional cerebral blood flow (rCBF) and the binding of central type benzodiazepine receptors (BZR) in infarction by means of permanent occlusion of the unilateral middle cerebral arteries (MCA) in rat. Iodine-125 Iomazenil and 99mTc-HMPAO was used to label BZR and rCBF respectively. In the chronic phase of infarction 21 to 28 days after occlusion (5 rats), rCBF in the left MCA territory was decreased to 62% of the sham control (4 rats), while BZR was more decreased to 45% of the control. In remote areas from the MCA lesion, the ipsilateral thalamus showed 28% decrease of BZR as compared to the control, though the decrease of rCBF was not significant. Iomazenil distribution may represent neuron density or BZR density on a neuron, since central type BZR is reported to be located on neurons. These results suggest that central type BZR imaging is more useful tool for the evaluation of brain tissue viability and transneuronal degeneration than rCBF imaging in brain infarction.

[Evaluation of the internal mammary nodes by lymphoscintigraphy and ultrasonography in patients with breast cancer].

The efficacy of lymphoscintigraphy and ultrasonography was evaluated in the detection of internal mammary lymph node (IMN) metastases in patients with breast cancer. On histological examination of IMN, 10 patients had metastases (positive group) and 47 did not (negative group). On lymphoscintigraphy, lack of uptake in the parasternal region of the affected side was classified as abnormal. The frequency of this abnormal finding was not significantly different between both groups. On sonography, the thickness of the sonolucent internal mammary area was measured. The thickness of the affected side was 6 mm or more in two patients of the positive group and only one of the negative group. A thickness of over 6 mm on the affected side was statistically significant (p less than 0.05). The difference in thickness between the affected side and the healthy side was 3 mm or more in four patients of the positive group, and was less than 3 mm in all patients of the negative group. A difference in thickness of more than 3 mm between the two sides was extremely significant (p less than 0.001). In conclusion, sonography is valuable in detecting IMN metastases, while lymphoscintigraphy is not useful. Sonography is recommended as an efficient diagnostic modality for IMN metastases.

[Myocardial perfusion and clearance of 99mTc teboroxime assessed by SPECT].

99mTc teboroxime is a new myocardial imaging agent that has characteristics of high accumulation in the heart and rapid clearance. We performed tomographic teboroxime study and compared the findings with that of 201Tl. Myocardial teboroxime clearance was calculated by dynamic single photon emission computed tomography (SPECT) using continuous repetitive rotation acquisition method. Teboroxime SPECT image was reconstructed by the three-minute data started from 4 minutes after injection. In 45 myocardial regions (15 patients), complete agreement between 201Tl and 99mTc teboroxime was obtained in 33 regions (73%), when the findings were classified as normal, ischemia and infarction. Significant delay in clearance was seen in the region of coronary stenosis (greater than or equal to 75%) compared with that in the control region (p = 0.0087 at rest, and p = 0.0385 at peak exercise by paired T test). Septum-to-lateral ratios of the clearance and myocardial initial count showed positive correlation (r = 0.743). Further clinical application of this radiopharmaceutical is expected as a new myocardial imaging agent.

[Characteristics of the myocardial SPECT images of 99mTc-MIBI and 99mTc-teboroxime].

Characteristics of the myocardial distribution of 99mTc-MIBI and 99mTc-Teboroxime was compared with the myocardial distribution of 201Tl. We made summed myocardial images, in which central three short-axis SPECT slices were added. Rectangular region of interest (ROI) was set on each myocardial segment, and mean counts of each myocardial region was obtained using summed short-axis images. The ratio of inferior-to-anterior mean counts (I/A) was 0.69 +/- 0.20 in 99mTc-MIBI and 0.62 +/- 0.16 in 201Tl. The ratio of inferior-to-lateral mean counts was 0.70 +/- 0.18 and 0.65 +/- 0.13, respectively. Both ratios in 99mTc-MIBI were significantly higher than those in 201Tl (p less than 0.05). 201Tl to 99mTc-MIBI ratios of these two values were 1.11 +/- 0.17 (I/A) and 1.08 +/- 0.16 (I/L). The ratios of I/A and I/L of 99mTc-MIBI were about 10 percent higher than those of 201Tl. 99mTc-Teboroxime dynamic short-axis SPECT images of every three-minute were obtained. The ratios of counts in each wall were calculated similarly. After about 8 minutes, gradual increase in hepatic activity can be a cause of quantitative error in the assessment of SPECT images. We obtained the data with a human cardiac phantom. The myocardial phantom filled with 99mTc or 201Tl was placed in the mediastinal portion that is surrounded by the lung (saw dust) and vertebra (plastic bar). The ratio of I/A was 0.79 and I/L was 0.85 in 201Tl. The I/A ratio was 0.93 and I/L was 0.97 in 99mTc. Both ratios in 99mTc were about 15 percent higher than those in 201Tl.(ABSTRACT TRUNCATED AT 250 WORDS)

[Lung ventilation imaging with TECHNEGAS: clinical study of lung deposition and ventilation/perfusion].

In order to optimize inhalation method for lung ventilation imaging with Tc-99m-gas (TECHNEGAS), relation between lung deposition of TECHNEGAS and inhalation method was evaluated. Submaximal inhalation with breath-holding (BH), continuous submaximal inhalation (C) and tidal inhalation (TV) were compared in 35 patients (36 studies) with various lung diseases. Mean lung deposition of TECHNEGAS was 6.6-7.4%/LD in BH group and was significantly higher than other groups of inhalation method (p less than 0.05-0.001). Lung deposition increased according to the times of inhalation in C group. TV group resulted in the lowest lung deposition which was same as 5 times of inhalation in C group. Lung/filter ratio (L/F) was highest in BH group. Image quality of TECHNEGAS was significantly better in BH group. Hot spot in central airway was seen in 15% of patients. All of them was in TV or C groups. In order to improve lung deposition and image quality of the TECHNEGAS, sufficient breath-holding was important. L/F seemed to be the index of effective inhalation of the TECHNEGAS. TV was suitable for poorly cooperative or dyspneic patients. TECHNEGAS was useful for evaluation of lung ventilation to provide good quality image with safety and simplicity.