The superacute stage of focal ischemia can be visualized using T₂-weighted MRI following the injection of superparamagnetic iron oxide particles (magnetite). In this study we evaluated the optimal time point, i.e. the time producing the strongest signal, for the injection of magnetite using T₂-weighted MRI following left parmanent middle cerebral artery occlusion (lt.-PMCAO). Male Sprague-Dawley rats were anesthetized and the left middle cerebral artery (lt.-MCA) was permanently occluded. Magnetite was then injected into the femoral vein after 20 to 30 min of It.-PMCAO. T₂-weighted MR images were taken immediately, and 15 and 30 min after magnetite injection. A high signal area at the region of the It.-MCA was clearly seen on the T₂-weighted MRI immediately after magnetite injection. However, it became less clear after 15 min, and by 30 min could not be distinguished. These results suggest that magnetite should be injected immediately prior to T₂-weighted MR imaging during the superacute stage of focal ischemia. (J Nippon Med Sch 1998; 65: 135-139)

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In order to further understand the pathology of Alzheimer's disease (AD), we have utilized image analysis in diagnosing the early stages of AD in patients with cognitive disorders. CT and MRI, however, have not been feasible since only atrophy is seen and it is difficult to differentiate the changes in AD from age associated changes. In this study we tried to determine whether regional cerebral blood flow (rCBF) measurements using single photon emission CT (SPECT) are feasible for the early diagnosis of AD. Regional CBF (rCBF) was measured using SPECT in three subject groups : Age-associated memory impairment (AAMI. n-9), mild AD (n=16), and normal aged patients (mean age=68.3 ; n=20). The subjects were then observed for three years. The region of interest (ROI) for the medial temporal lobe was set at OM-30° to cover the maximum area of the hippocampus. The absolute values of rCBF in the frontal, temporal, and parietal lobes and the cerebellum were significantly lower in the mild AD subjects than in the normal aged subjects. A significant decrease in rCBF was also seen in the medial temporal lobe in both the AD and the AAMI subjects compared to the normal controls. During the three years of follow up, no cases of dementia were seen in the AAMI subjects. However, there were two patients who appeared to have difficulty in adapting to daily life due to amnesia, one with a decrease in rCBF of the medial temporal lobe on the second SPECT, and the other showing a low rCBF the first time.
This study suggests that AAMI subjects may comprise both AD and normal subjects. Therefore a more prospective study is needed. (J Nippon Med Sch 1998; 65: 140-147)

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Thrombolytic therapy during the hyperacute stage is important for salvaging dying cerebral tissue. To date, however, accurate non-invasive assessment of an ischemic lesion during the hyperacute stage has not been possible. Perfusion MRI may be the key to the quick diagnosis of ischemic lesions. To assess the feasibility of dynamic contrast enhanced perfusion MRI, echo planar imaging was performed in 10 patients with ischemic stroke. The relative cerebral blood volume (rCBV), mean transit time (MTT), and relative cerebral blood flow(rCBF) were measured based on moment analysis and the gamma variate method. These measurements, however, are not suitable for the detection of cerebral ischemia during the hyperacute stage. Therefore, we additionally studied the changes in a concentration curve (time-ΔR^* curve) of Gd-DTPA, injected into the median vein of the forearm. From the curve the SUM (ΔR^*) time to peak and the ΔR^* peak, which may be calculated quickly, were determined and were compared to rCBV, MTT, and rCBF, respectively. The rCBV and the rCBF in the ischemic regions were less than those in the contralateral healthy regions (p<0.05), and the MTT in the ischemic regions was longer than that in the contralateral healthy regions (p<0.05). Additionally, SUM (ΔR^*) and the ΔR^* peak in the ischemic regions were less, and the time to peak in the ischemic regions was longer than the value in the contralateral healthy regions (p<0.05), correlating well to the rCBV, rCBF, and MTT measurements. Also, images of these parameters, depicting the ischemic lesion earlier than conventional T2 weighted images, can be easily made by using an MRI console. These results suggest that the SUM (ΔR^*), time to peak and the ΔR^* peak images calculated with dynamic contrast enhanced perfusion MRI may be one of the best techniques for the detection of cerebral ischemic lesions during the hyperacute stage. (J Nippon Med Sch 1998; 65: 148-154)

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Background : Intron 16 insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene may be associated with the progression of renal insufficiency in patients with renal diseases. The objective of this study was to determine whether D allele is a risk factor for the progression of the disease in end-stage renal disease (ESRD) patients.
Methods : Using PCR techniques, genetic analysis of the ACE I/D polymorphism was performed on 326 dialysis patients. We compared the distribution of genotypes and allele frequency of this polymorphism in dialysis patients and the normal Japanese population. The clinical courses of 47 patients were studied retrospectively, and the progression of chronic renal failure using time plots of the reciprocal of serum creatinine (1/Cr) was estimated.
Results and Conclusion : The frequencies for II, ID, and DD genotypes were 134, 148 and 44, respectively. The frequency for I allele was 0.64, and for D allele 0.36. These results were similar to the frequencies found in the normal Japanese population. However, patients with polycystic kidney disease (PKD) showed a high frequency for D allele (0.54: p=0.023 by x² method). In longitudinal courses, we did not find any association between ACE gene polymorphism and the declining rate of renal function. However, in patients with PKD, the DD genotype may influence the clinical course of renal disease. (J Nipi on Med Sch 1998: 65: 155-160)

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Quinolinic acid (QA), a tryptophan metabolite, is known to be present in many regions of the mammalian central nervous system (CNS). However, its role is stir unclear. In order to evaluate the physiological role of QA in CNS, the present study was undertaken to examine its action on the spinal motoneurons of newborn rats in vitro. It was found that QA depolarized spinal motoneurons directly. Its potency was the same as that of glutamic acid at the same concentrations. The depolarization induced by QA was strongly inhibited by 2-amino-5-phosphonovalerate (AP5), an NMDA receptor antagonist. The effect of quinolinic acid was, on the other hand, not inhibited by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), a non-NMDA receptor antagonist, in the presence of glycine. These results indicate that the NMDA receptor is responsible for the QA-induced-depolarization. The possible role of QA as a transmitter is discussed. (J Nippon Med Sch 1998 ; 65: 161-166)

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Purpose : To investigate changes in both water diffusion coefficients and diffusion anisotropy in white matter of non-demented patients with leuko-araiosis using diffusionweighted MRI.
Methods : Diffusion mapping was performed on 8 non-demented patients with leukoaraiosis, 6 patients with chronic cerebral infarction and 6 healthy volunteers, using a spinecho sequence with motion probing gradient applied sequentially at two gradient strength settings in three orthogonal directions. The apparent diffusion coefficients (ADC) were calculated from 4 regions of interest located within the frontal and parietal subcortical white matter. The index of diffusion anisotropy (IDA) was calculated from the ADC in three orthogonal directions. (IDA=ADCmax-min/ADCmean×100)
Results : Significantly larger ADC were found within the frontal and parietal subcortical white matter in the non-demented patients with leuko-araiosis (mean=1.51±0.36×10^-3mm²/s) and the were also significantly larger in patients with cerebral infarction (mean=2.12±0. 46×10^-3mm²/s) than in the control group (mean =1.01±0.33×10^-3mm²/s). But no significant differences were found in the IDA between the non-demented patients with leuko-araiosis (mean=43.1±29.2) and the control group (mean= 46.5±32.5).
Conclusion : An increase in extracellular space caused by the loss of axonal fibers and myelin is probably the cause of the higher ADC in periventricular hyperintensity lesions. However, the remaining nerve fibers maintain the anisotropy in the lesions in non-demented patients with leuko-araiosis. (J Nippon Med Sch 1998; 65: 167-172)

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