Hiroo Ikehira

Brain N-acetylaspartate is elevated in Pelizaeus-Merzbacher disease with PLP1 duplication.

Objective: To assess alterations in brain metabolites of patients with Pelizaeus–Merzbacher disease (PMD) with the proteolipid protein gene 1 (PLP1) duplications using quantitative proton MRS. Methods: Five unrelated male Japanese patients with PMD with PLP1 duplications were analyzed using automated proton brain examination with the point resolved spectroscopy technique (repetition and echo time of 5,000 and 30 msec). Localized spectra in the posterior portion of the centrum semiovale were acquired, and absolute metabolite concentrations were calculated using the LCModel. Results: Absolute concentrations of N-acetylaspartate (NAA), creatine (Cr), and myoinositol (MI) were increased by 16% (p < 0.01), 43% (p < 0.001), and 31% (p < 0.01) in patients with PMD as compared with age-matched controls. There was no statistical difference in choline concentration. Conclusion: The increased concentration of NAA, which could not be detected by previous relative quantitation methods, suggests two possibilities: axonal involvement secondary to dysmyelination, or increased cell population of oligodendrocyte progenitors. Elevated Cr and MI concentrations may reflect the reactive astrocytic gliosis. Our study thus emphasizes the importance of absolute quantitation of metabolites to investigate the disease mechanism of the dysmyelinating disorders of the CNS.

Distinctly abnormal brain metabolism in late-onset ornithine transcarbamylase deficiency

Objective To assess alterations in brain metabolites in patients with late-onset ornithine transcarbamylase deficiency (OTCD). Methods Six unrelated, asymptomatic Japanese late-onset OTCD patients were analyzed by proton MRS (1HMRS) using a point-resolved spectroscopy technique (repetition and echo times, 5000 and 30 ms). Localized spectra for the centrum semiovale were acquired and absolute metabolite concentrations were calculated using an LCModel. Results Compared with age-matched controls, N-acetylaspartate and creatine concentrations were normal in all patients. The glutamine (Gln) plus glutamate concentration was increased in four patients, which progressed in proportion to the clinical stage. myo-inositol (mI) could not be detected in five symptomatic patients. A decreased choline (Cho) concentration was detected in two clinically severe patients. 1HMRS after liver transplantation in one patient revealed the normalization of all metabolites. Conclusion These findings suggest progression of neurochemical events in OTCD, i.e., mI depletion and Gln accumulation followed by Cho depletion, which is reverse of that in hepatic encephalopathy, i.e., Cho depletion followed by mI depletion and Gln accumulation.

Three-vessel study of cerebral blood flow using phase-contrast magnetic resonance imaging: Effect of physical characteristics

The development of phase-contrast magnetic resonance imaging (P-C MRI) provides a noninvasive method for measurement of volumetric blood flow (VFR). We performed P-C MRI to study the effects of physical characteristics on cerebral blood flow. VFR of the left and right internal carotid arteries and basilar artery were measured using P-C MRI and total cerebral blood flow (tCBF) was calculated by summing up the VFR values in the three vessels. Moreover, we investigated the changes in these blood flows as influenced by age, head size, height, weight, body surface area, and handedness. The blood flows were 142 +/- 58 ml/min (mean +/- standard deviation) in the basilar artery; and 229 +/- 86 ml/min in the left, and 223 +/- 58 ml/min in the right internal carotid artery; and tCBF was 617 +/- 128 ml/min. Significant increases were observed in head size-related change of VFR in the basilar artery (p = .028) and height-related change of tCBF (p = .045). The other characteristics did not significantly influence any VFR. The results suggest that head size and height may reflect CBF, and that these effects should be considered when changes of CBF are diagnosed. Phase-contrast MRI is useful for a noninvasive and rapid analysis of cerebral VFR and has potential for clinical use.

Seizure frequency and bilateral temporal abnormalities: a proton magnetic resonance spectroscopy of temporal lobe epilepsy

Proton magnetic resonance spectroscopy ((1)H-MRS) was performed in seven healthy volunteers and 17 patients with temporal lobe epilepsy (TLE) to clarify the correlation of the severity of epilepsy with bilateral temporal changes in N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine + phosphocreatine (Cr). Despite unilateral EEG focus, bilateral temporal reduction in NAA /(Cho + Cr) was revealed in patients with intractable seizures. The potential for seizure generation correlated with the NAA /(Cho + Cr) reduction not only on the ipsilateral side but also on the contralateral side. Proton MRS proved to be a useful measurement for obtaining important information about the neuronal changes as well as the lateralization of the epileptogenic focus in TLE patients.

Proton MR Spectroscopy in Solvent Abusers

Chronic solvent abuse is known to cause neurologic sequelae including cognitive, pyramidal and brain stem/cerebellar dysfunction.’ Magnetic resonance imaging (MRI) studies revealed diffuse white matter changes on T2-weighted images in the central nervous s y ~ t e m . ~ . ~ These TZprolonged lesions may represent demyelination, myelin pallor and gliosis reported in previous pathological studies.2.4.5 However, it is not easy to distinguish these pathologies, using conventional neuroimaging methods. Recently, a study on various demyelinating diseases suggested that the changes in cerebral metabolites detected by proton MR spectroscopy (MRS) may reflect histopathological changes.6 The aim of this preliminary study is to elucidate the histopathological nature of the T2-prolonged lesion in the white matter of chronic solvent abusers using proton MR spectroscopy.

The measurement of blood flow parameters with deuterium stable isotope MR imaging.

MethodsBecause there are no radioactive hydrogen isotopes which can be used for clinical examinations, deuterium as a non-radioactive, freely diffusible tracer has some advantages compared with the radioactive tracers in the measurement of blood flow parameters. A non-invasive technique to estimate the mean tissue blood flow parameterin vivo was developed by using deuterium nuclear magnetic resonance (NMR) imaging in rat. We obtained the NMR signal changes from deuterium NMR images in nine male Wister rats after intravenous injection of D2O and applied exponential curve fitting analyses to calculate blood flow parameters of the brain, heart and skeletal muscle.ResultsWhile fitting the reducing of the monoexponential function yielded a blood flow parameter of 27.9 ± 1.6 ml/min/100 g tissue weight for the brain and 46.7 ± 3.7 ml/min/100 g tissue weight for the heart, fitting the early reducing of the signal intensity of the biexponential function yielded a blood flow parameter of 95.6 ± 10.9 ml/min/100 g tissue weight for the brain and 108.0 ±13.1 ml/min/100 g tissue weight for the heart. The mean muscle blood flow parameter determined by the monoexponential uptake function was 43.8 ± 7.3 mZ/min/100 g tissue weight. Conclusions: The blood flow parameter measurement by means of an imaging coil for deuterium is less invasive and reflects the mean tissue blood flow parameter for the entire tissue sample more homogeneously than spectroscopic monitoring.

Evaluation of blood flow patterns of true and false lumens in dissecting aneurysms using MR phase-contrast techniques

The magnetic resonance phase-contrast technique for the measurement of flow velocity and volume in true and false lumens was studied in six patients with chronic dissecting aneurysms. Phase-contrast images were obtained at a level perpendicular to the dissecting aneurysms of the descending aorta. As the maximum diameter of aneurysms increased, the ratio of the cross-sectional area of the false to the true lumen increased and the peak average velocity in the true lumen during systole was decreased. This technique proved invaluable for determining prognosis and operability for this condition.

Photon-deficient bone metastases in hepatocellular carcinoma.

Photon deficient areas on bone scans in bone metastases from hepatocellular carcinoma (HCC) have been reported previously. In this report, three different patterns of photopenia in patients with metastatic HCC are seen. Areas of increased uptake as well as photon deficient areas were seen in the metastatic areas on bone imaging.

Magnetic resonance imaging of reticulo‐endothelial system in patients with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is characterized by accelerated platelet destruction in the reticulo‐endothelial system (RES). We performed magnetic resonance imaging (MRI) to estimate the degree of activated RES. MRI was performed with a Gyroscan S‐15 (1.5 tesla) in 7 healthy volunteers and 22 patients with ITP. The 22 patients included 19 who were at initial diagnosis or were nonresponders to the therapy (non‐DX group), and 3 who were responders. For the non‐DX group, the T1 relaxation time of the spleen was initially significantly shorter than for healthy volunteers, but normalized after responding to the therapy. The initially shorter T1 values of the spleen for ITP patients correlated with a low platelet count (P < 0.05). This condition may indicate foam cells or fatty components due to platelet destruction. There was no significant relationship between the sequestration in 111In‐scan and T1 values of the liver or spleen. However, MRI is a noninvasive method, and it may be a clinically useful tool in the evaluation of RES in patients with ITP. Am. J. Hematol. 56:52–58, 1997.