Kazuhiro Homma

Stable nitroxide Tempol ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischemia.

Oxygen free radicals have been implicated in the pathogenesis of cerebral ischemia and reperfusion injury. 4-Hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (Tempol) has been reported as a stable nitroxide and a membrane-permeable free radical scavenger. This study was performed to investigate the mechanism of Tempol in attenuating ischemia-reperfusion injury in a rat model of transient focal cerebral ischemia. We measured the cerebral 2,3-dihydroxybenzoic acid (DHBA) level as the amount of hydroxyl radical production using a microdialysis technique with salicylic acids trapping during ischemia and reperfusion. The concentration of cerebral thiobarbituric acid reactive substances (TBARS), representing the extent of lipid peroxidation by free radicals, and the area of cerebral infarction were also measured. The level of cerebral 2,3-DHBA was increased during ischemia and reperfusion, especially during the early reperfusion stage at the periphery of the infarct area (nearly 500-fold). Intravenous administration of Tempol at the time of reperfusion reduced 2,3-DHBA production (Vehicle group: 472.2+/-196.2, Tempol group: 238.3+/-77.2) and the cerebral TBARS level (Vehicle group: 541.7+/-84.7, Tempol group: 339.0+/-147.2 nmol/g), and decreased the size of the cerebral infarction (Vehicle group: 202.2+/-98.4, Tempol group: 98.5+/-13.7 mm(3)). In contrast, Tempol administered 15 min prior to reperfusion reduced neither the TBARS level nor the size of the infarction. These results indicate that Tempol administration at the time of reperfusion reduced lipid peroxidation by scavenging free radicals, resulting in a reduction of the infarct size.

Time-resolved diffuse optical tomographic imaging for the provision of both anatomical and functional information about biological tissue

We present in vivo images of near-infrared (NIR) diffuse optical tomography (DOT) of human lower legs and forearm to validate the dual functions of a time-resolved (TR) NIR DOT in clinical diagnosis, i.e., to provide anatomical and functional information simultaneously. The NIR DOT system is composed of time-correlated single-photon-counting channels, and the image reconstruction algorithm is based on the modified generalized pulsed spectral technique, which effectively incorporates the TR data with reasonable computation time. The reconstructed scattering images of both the lower legs and the forearm revealed their anatomies, in which the bones were clearly distinguished from the muscles. In the absorption images, some of the blood vessels were observable. In the functional imaging, a subject was requested to do handgripping exercise to stimulate physiological changes in the forearm tissue. The images of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentration changes in the forearm were obtained from the differential images of the absorption at three wavelengths between the exercise and the rest states, which were reconstructed with a differential imaging scheme. These images showed increases in both blood volume and oxyhemoglobin concentration in the arteries and simultaneously showed hypoxia in the corresponding muscles. All the results have demonstrated the capability of TR NIR DOT by reconstruction of the absolute images of the scattering and the absorption with a high spatial resolution that finally provided both the anatomical and functional information inside bulky biological tissues.

Characteristic signal intensity changes on postmortem magnetic resonance imaging of the brain

PurposeWe investigated and identified postmortem changes on magnetic resonance imaging (MRI) of the brain to provide accurate diagnostic guidelines.Materials and methodsOur subjects were 16 deceased patients (mean age 57 years) who underwent postmortem computed tomography (CT), MRI, and autopsy, the latter of which showed no abnormalities in the brain. The subjects underwent CT and MRI 6–73 h after confirmation of death (mean 26 h), after being kept in cold storage at 4°C. Postmortem MRI of the brain was performed using T1-weighted imaging (T1WI), T2WI, fluid attenuated inversion recovery (FLAIR) imaging, and diffusion weighted imaging (DWI) with parameters identical to those used for living persons.ResultsIn all cases, postmortem CT showed brain edema and swelling. Postmortem MRI showed characteristic common signal intensity (SI) changes, including (1) high SI of the basal ganglia and thalamus on T1WI; (2) suppression of fat SI on T2WI; (3) insufficient SI suppression of cerebrospinal fluid on FLAIR imaging; (4) high SI rims along the cerebral cortices and the ventricular wall on DWI; and (5) an apparent diffusion coefficient decrease to less than half the normal value.ConclusionPostmortem MRI of the brain in all cases showed characteristic common SI changes. Global cerebral ischemia without following reperfusion and low body temperature explain these changes.

Modeling shear modulus distribution in magnetic resonance elastography with piecewise constant level sets

Magnetic resonance elastography (MRE) is designed for imaging the mechanical properties of soft tissues. However, the interpretation of shear modulus distribution is often confusing and cumbersome. For reliable evaluation, a common practice is to specify the regions of interest and consider regional elasticity. Such an experience-dependent protocol is susceptible to intrapersonal and interpersonal variability. In this study we propose to remodel shear modulus distribution with piecewise constant level sets by referring to the corresponding magnitude image. Optimal segmentation and registration are achieved by a new hybrid level set model comprised of alternating global and local region competitions. Experimental results on the simulated MRE data sets show that the mean error of elasticity reconstruction is 11.33% for local frequency estimation and 18.87% for algebraic inversion of differential equation. Piecewise constant level set modeling is effective to improve the quality of shear modulus distribution, and facilitates MRE analysis and interpretation.

Microscopic laser Doppler velocimeter for blood velocity measurement

A high-resolution laser Doppler velocimeter with small measurement volume is described. This instrument uses a novel frequency shifter incorporating a moving glass prism that gives stable frequency shifts up to 7 kHz and determines the velocity measurement range, which is 0.1 to 7 mm/s. The instrument has been used to measure blood flow velocities in microvessels and results are presented that demonstrate the capabilities of the system.

Abnormal brain MRI signal in 18q-syndrome not due to dysmyelination

BACKGROUND 18q-Syndrome is a chromosomal disorder exhibiting various symptoms arising from the central nervous system. Brain magnetic resonance imaging (MRI) of patients with this syndrome usually demonstrates abnormal white matter intensities. This is widely believed to be due to impaired myelin formation because this syndrome involves the deletion of the myelin basic protein (MBP) gene in 18q23. However, this hypothesis has not been confirmed by actual pathology because early death is unusual and autopsy rarely performed. PATIENT A 6-year-old boy with ring chromosome 18 syndrome was examined by genetic analysis for the MBP gene, brain MRI, and autopsy. RESULTS Haploinsufficiency of the MBP gene was confirmed. T(2)-weighted MRI revealed diffuse high intensities throughout the cerebral white matter. Pathological examination showed the cerebral white matter to be uniformly stained by Klüver-Barrera and MBP immunohistochemical staining. Oligodendrocytes were immunoreactive for proteolipid protein and ferritin but not MBP. Electron microscopy revealed clusters of axons wrapped in compact myelin sheaths with distinct major dense lines. Holzer and immunohistochemical staining for glial fibrillary acidic protein showed extensive staining of the white matter and an increased number of glial filaments. CONCLUSIONS This pathological study demonstrated that in this disorder, the brain was well myelinated, contrary to established hypotheses about this disorder. The MRI signal abnormalities in 18q-syndrome could be attributed to gliosis and not to dysmyelination.

Evaluation of negative fixed-charge density in tissue-engineered cartilage by quantitative MRI and relationship with biomechanical properties

Applying tissue-engineered cartilage in a clinical setting requires noninvasive evaluation to detect the maturity of the cartilage. Magnetic resonance imaging (MRI) of articular cartilage has been widely accepted and applied clinically in recent years. In this study, we evaluated the negative fixed-charge density (nFCD) of tissue-engineered cartilage using gadolinium-enhanced MRI and determined the relationship between nFCD and biomechanical properties. To reconstruct cartilage tissue, articular chondrocytes from bovine humeral heads were embedded in agarose gel and cultured in vitro for up to 4 weeks. The nFCD of the cartilage was determined using the MRI gadolinium exclusion method. The equilibrium modulus was determined using a compressive stress relaxation test, and the dynamic modulus was determined by a dynamic compression test. The equilibrium compressive modulus and dynamic modulus of the tissue-engineered cartilage increased with an increase in culture time. The nFCD value--as determined with the [Gd-DTPA(2-)] measurement using the MRI technique--increased with culture time. In the regression analysis, nFCD showed significant correlations with equilibrium compressive modulus and dynamic modulus. From these results, gadolinium-enhanced MRI measurements can serve as a useful predictor of the biomechanical properties of tissue-engineered cartilage.

Ultrasonic Measurement of Fluid Viscosity for Blood Characterization

Although plaque rupture in arteriosclerosis is affected by not only its strength but also by hemodynamic factors, such as blood pressure and shear stress, in particular, the viscous coefficient which directly controls the magnitude of shear stress might be a risk factor in plaque rupture. Therefore, if the viscous coefficient can be assessed noninvasively, it can be a useful index for prediction of a plaque rupture and assessment of various diseases. In this work, an ultrasonic methodology to estimate the viscous coefficient was investigated by numerical simulation and flow-phantom experiment as the fundamental investigation for noninvasively assessing the viscous characteristics of blood. These results show that the proposed method is useful for estimating the kinematic viscosity coefficient in the viscous evaluation of blood.

A simple method for MR elastography: a gradient-echo type multi-echo sequence

To demonstrate the feasibility of a novel MR elastography (MRE) technique based on a conventional gradient-echo type multi-echo MR sequence which does not need additional bipolar magnetic field gradients (motion encoding gradient: MEG), yet is sensitive to vibration. In a gradient-echo type multi-echo MR sequence, several images are produced from each echo of the train with different echo times (TEs). If these echoes are synchronized with the vibration, each readouts gradient lobes achieve a MEG-like effect, and the later generated echo causes a greater MEG-like effect. The sequence was tested for the tissue-mimicking agarose gel phantoms and the psoas major muscles of healthy volunteers. It was confirmed that the readout gradient lobes caused an MEG-like effect and the later TE images had higher sensitivity to vibrations. The magnitude image of later generated echo suffered the T2 decay and the susceptibility artifacts, but the wave image and elastogram of later generated echo were unaffected by these effects. In in vivo experiments, this method was able to measure the mean shear modulus of the psoas major muscle. From the results of phantom experiments and volunteer studies, it was shown that this method has clinical application potential.

Hepatic Relaxation Times from Postmortem MR Imaging of Adult Humans

Purpose: To measure T1 and T2 values of hepatic postmortem magnetic resonance (PMMR) imaging. Materials and Methods: We performed hepatic PMMR imaging of 22 deceased adults (16 men, 6 women; mean age, 56.3 years) whose deaths were for reasons other than liver injury or disease at a mean of 27.7 hours after death. Before imaging, the bodies were kept in cold storage at 4°C (mean rectal temperature, 17.6°C). We measured T1 and T2 values in the liver at two sites (the anterior segment of the right lobe and the lateral segment of the left lobe). We also investigated the influence of the body temperature and postmortem interval on T1 and T2 values. Results: In the anterior segment of the right lobe and the lateral segment of the left lobe, T1 values of PMMR imaging were 524 ± 112 ms and 472 ± 104 ms (mean ± standard deviation), respectively; while T2 values were 42 ± 6 ms and 43 ± 8 ms, respectively. T1 and T2 values did not differ significantly between the two sites (P ≧ 0.05). Regarding temperature, the T2 values of hepatic PMMR imaging were linearly correlated with the body temperature, but the T1 values were not. The T1 and T2 values of the two sites in the liver did not correlate with the postmortem interval. Conclusion: Reduction in body temperature after death is considered to induce T1 and T2 value changes in the liver on PMMR imaging.