Naoyuki Miyasaka

Different Apparent Diffusion Coefficient Water Content Correlations of Gray and White Matter During Early Ischemia

BACKGROUND AND PURPOSE Early and accurate diagnosis of brain edema in stroke patients is essential for the selection of appropriate treatment. We examined the correlations between the changes in the apparent diffusion coefficient (ADC), regional water content, and tissue ultrastructure during early focal cerebral ischemia. METHODS The left middle cerebral arteries of cats were occluded with an intramagnet occlusion/recirculation device. T2-weighted, diffusion-weighted, and perfusion imaging were performed repeatedly during the initial 3 hours after occlusion. The ADCs obtained from ADC maps were compared with the corresponding tissue water content values determined by gravimetry and electron microscopic water localization. RESULTS ADC reduction was detected in areas of low perfusion 15 minutes after occlusion and thereafter. The water content increase correlated linearly with the ADC decreases in both the gray and white matter. However, both the water content corresponding to an ADC value and the rate of ADC change of the gray and white matter differed significantly (P<.05) as follows: y = -10105x + 8533 (r=.86) and y = -6174x + 4611 (r=.67), respectively, where x is the water content (grams water per gram tissue) and y is the ADC (x 10(-6) mm2/s). Hydropic astrocytic swelling was seen in both structures, and in the white matter, oligodendroglial and myelinated axonal swelling and periaxonal space enlargement were observed. CONCLUSIONS When early ischemic edema in experimental focal cerebral ischemia is evaluated with ADC mapping, the different slopes and intercepts of the water content and ADC correlation lines for the gray and white matter, which probably reflect different ultrastructural localization of water, should be taken into account.

Differentiation between completely hyalinized uterine leiomyomas and ordinary leiomyomas: Three-phase dynamic magnetic resonance imaging (MRI) vs. diffusion-weighted MRI with very small b-factors

To assess the possibility of differentiating between completely hyalinized leiomyomas and ordinary leiomyomas by using diffusion‐weighted (DW) magnetic resonance imaging (MRI) (DWI) employing very small b‐factors (b = 1.51 and 55.3 seconds/mm2) in comparison with three‐phase dynamic MRI.

Ultrastructural and MRI study of the substantia nigra evolving exofocal post‐ischemic neuronal death in the rat

To clarify the morphological characteristics of exofocal post‐ischemic neuronal death (EPND) in the substantia nigra (SN), we investigated the course of light‐ and electron‐microscopic changes of the SN of rats subjected to occlusion of the left middle cerebral artery (MCA) for 1, 2, 4, 7 and 12 days. To assess cellular edema, sequential magnetic resonance (MR) mapping of the apparent diffusion coefficient (ADC) and the T2 value test was performed. Histological and electron‐microscopic examination on day 1 showed dotted chromatin clumps in the nuclei of some neurons and mild swelling of the perivascular endfeet of astrocytes in the ipsilateral SN. On day 2, a few cells of the ipsilateral SN pars reticulata (SNr) revealed key morphological signs of apoptosis – apoptotic body‐like condensation and segregation of the chromatin and DNA fragmentation‐like nuclear remnants. On day 4, 38% of neurons became swollen (pale neurons) with cytoplasmic microvacuoles, which appeared to originate from rough endoplasmic reticulum (rER), mitochondria and Golgi apparatus. Twenty percent of neurons showed massive proliferation of the cisternae of the rER, some of which were fragmented or had lost their normal parallel arrangement. In addition, MR mapping revealed a transient ADC decrease with a T2 increase (signifying a phase of cellular edema), which coordinated with the phase of ultrastructural cellular swelling. Further, the total number of neurons started to decrease gradually, the perivascular endfeet of astrocytes were markedly swollen, and the neuropil became loose on day 4. On day 7, reactive astrocytes and dark neurons occurred most frequently. These results suggest that the EPND in the SN after occlusion of the MCA in adult rats is due to both apoptosis and necrosis, although necrosis seems to be the dominant mechanism of the EPND. However, the morphologic resemblances of EPND to delayed neuronal death suggest these processes have a common pathomechanism.

Characteristic changes in T2-value, apparent diffusion coefficient, and ultrastructure of substantia nigra evolving exofocal postischemic neuronal death in rats

To correlate the magnetic resonance (MR) imaging characteristics of exofocal postischemic neuronal death (EPND) in the substantia nigra (SN) with associated histologic changes, we occluded the left middle cerebral artery of rats for 1, 4, 7, or 12 days. Day 1 (post-occlusion) T(2)-weighted images revealed high signal intensity indicative of infarction in the ipsilateral caudate nucleus, putamen, and cortex but not the SN. Diffusion-weighted images (DWIs) on day 1 similarly failed to reveal any changes in the SN. However, on day 4, DWIs revealed high signal intensity in the ipsilateral SN, in which the apparent diffusion coefficient (ADC) transiently decreased (P<0.05) while the T(2)-value increased (P<0.05). These measures returned to and remained at control levels on days 7 and 12. Histologic examination on day 4 revealed dark-staining neurons, markedly swollen perivascular astrocytic end-feet, many swollen neurons with cytoplasmic microvacuoles that mainly originated in the rough endoplasmic reticulum, and strongly roughed neuropils. Reactive astrocytes and dark neurons most frequently appeared on days 7 and 12. The severity of cellular swelling paralleled the change in the ADC. These results demonstrate that a transient high-intensity signal on DWIs, indicative of a decrease in the ADC, is predictive of EPND in the SN.

Efficacy of recombinant annexin 2 for fibrinolytic therapy in a rat embolic stroke model: A magnetic resonance imaging study

Efficacy of recombinant annexin 2 (rAN II) in a rat model of embolic stroke was examined using a magnetic resonance imaging (MRI) and histology. The right middle cerebral artery of male Wistar rats was occluded by autologous clots under anesthesia. Four doses of rAN II (0.125, 0.25, 0.5 and 1.0 mg/kg, n=10 for each group) or saline (1 ml/kg, n=10) were administrated intravenously within 5 min before clot infusion. Serial changes in apparent diffusion coefficient (ADC) and relative blood flow (CBF) were measured with the use of MRI in half of the animals in each group. The remaining half of the animals in each group was evaluated for hemorrhage and final infarct size by histology at 48 h after embolization. At 3 h after embolization, lesion volumes with ADC were abnormality and CBF in the peripheral lesion was improved in groups treated with 0.25, 0.5 and 1.0 mg/kg, but not 0.125 mg/kg, of rAN II in comparison with the saline-treated group (P<0.05). Histological analyses were consistent with MRI findings. More importantly, no hemorrhagic transformation was documented in rats treated with 0.125 and 0.25 mg/kg of rAN II, whereas it was observed at higher doses. We concluded that rAN II at 0.25 mg/kg significantly reduced infarct size and improved CBF without hemorrhagic complications. rAN II is a novel compound that has the potential to be a promising fibrinolytic agent to treat embolic stroke.

Diffusion‐tensor MRI and tractography of the esophageal wall ex vivo

To demonstrate the feasibility of diffusion‐tensor magnetic resonance imaging (MRI) and tractography as a means of evaluating the individual layers of the normal esophageal wall by using esophageal specimens containing carcinoma.

Emotional state and coping style among gynecologic patients undergoing surgery

Abstract  The aim of the present study was to investigate changes in emotional state and the relationship between emotional state and demographic/clinical factors and coping style among gynecologic patients undergoing surgery. Using the Japanese version of the Profile of Mood States (POMS), 90 patients (benign disease: 32, malignancy: 58) were examined on three occasions: before surgery, before discharge, and 3 months after discharge. They were also examined using the Coping Inventory for Stressful Situations (CISS) on one occasion before discharge. The scores for the subscales depression, anger, and confusion were the highest after discharge while those for anxiety were the highest before surgery. The average scores of the POMS subscales for all subjects were within the normal range. With regard to the relationship between these emotional states and other factors, multiple regressions showed that the principal determinants of anxiety before surgery were religious belief, psychological symptoms during hospitalization and emotion‐oriented (E) coping style; further, it was found that depression after discharge could be explained by chemotherapy, duration of hospitalization, and E coping style. The principal determinants of anger after discharge and vigor before surgery were length of education and E coping style, and severity of disease, chemotherapy, E coping style and task‐oriented coping style, respectively. Those of post‐discharge fatigue and confusion were length of education, psychological symptoms, and E coping style. In summary it is suggested that the following should be taken into account in patients undergoing gynecologic surgery: anxiety before surgery, depression, anger, and confusion after surgery, including coping styles.

Transient ADC change precedes persistent neuronal death in hypoxic–ischemic model in immature rats

A brief ischemia causes delayed neuronal death (DND) in some areas vulnerable to ischemia. Additionally, it causes a transient reduction in the apparent diffusion coefficients (ADCs) obtained from diffusion-weighted magnetic resonance imaging (DWI), which is a powerful tool to detect ischemic changes in the brain at a very early stage. The present study examined long-term histopathological changes in the hippocampal neurons up to 30 days after a very mild hypoxic-ischemic (HI) insult in immature rats. Three-week-old male rats were subjected to 15- and 30-min HI insults (15-min HI and 30-min HI) and serial DWI was performed. Only animals whose ADC reduction pattern was transient were examined histopathologically. ADCs decreased significantly during the insult, and the ADC values of 30-min HI group were significantly lower than those of 15-min HI group. Ischemic neuronal changes were observed up to 30 days after the insult in 30-min HI group, although ADCs in the chronic stage were within the normal range. In addition, neuron density in 30-min HI group was significantly lower in the chronic stage (on days 14 and 30) than in 15-min HI group. A very mild hypoxia-ischemia followed by a transient ADC reduction causes persistent neuronal death, which can be predicted by measuring ADCs during the acute insult.

Esophageal Carcinoma: Ex Vivo Evaluation with Diffusion-Tensor MR Imaging and Tractography at 7 T

PURPOSE To determine the feasibility of diffusion-tensor magnetic resonance (MR) imaging and tractography as a means of evaluating the depth of mural invasion by esophageal carcinomas. MATERIALS AND METHODS This study was approved by the institutional review board, and written informed consent was obtained from each patient. Twenty esophageal specimens, each containing a carcinoma, were studied with a 7.0-T MR imaging system equipped with a four-channel phased-array surface coil. Diffusion-tensor MR images were obtained with a field of view of 50-60 mm × 25-30 mm, matrix of 256 × 128, section thickness of 1 mm, b value of 1000 sec/mm(2), and motion-probing gradient in seven noncollinear directions. The MR images were compared with the histopathologic findings as the reference standard. The differences in diffusion-tensor MR imaging parameters between the carcinoma and the layers of the esophageal wall were statistically analyzed by using the Dunnett test. RESULTS In all 20 carcinomas (100%), the diffusion-weighted images, apparent diffusion coefficient (ADC) maps, fractional anisotropy (FA) maps, λ1 maps, and direction-encoded color FA maps made it possible to determine the depth of tumor invasion of the esophageal wall that was observed during histopathologic examination. The λ1 maps showed the best contrast between the carcinomas and the layers of the esophageal wall. The carcinomas had both lower ADC values and lower FA values than the normal esophageal wall; thus, the carcinomas were clearly demarcated from the normal esophageal wall. Diffusion-tensor tractography images were also useful for determining the depth of tumor invasion of the esophageal wall. CONCLUSION Diffusion-tensor MR imaging and tractography are feasible in esophageal specimens and provide excellent morphologic data for the evaluation of mural invasion by esophageal carcinomas.

Time Course of Trace of Diffusion Tensor [Trace(D)] and Histology in Brain Edema

We examined the correlation between changes in the trace of diffusion tensor [Trace(D)], regional water content and tissue ultrastructure relating to cellular (cytotoxic) and vasogenic brain edema. Cellular edema was induced by left middle cerebral artery occlusion in cats (Kuroiwa T et al., 1998). Vasogenic edema was induced in the white matter of cats by a cold lesion (Kuroiwa T et al., 1999). In cellular edema, the water content increase correlated linearly with the Trace(D) decrease in both the gray and white matter. However, both the slopes and intercepts of the correlation lines were significantly different. Hydropic astrocytic swelling was seen in both structures, and in the white matter, oligodendrocytic and myelinated axonal swelling were observed. In vasogenic edema, the increase in Trace(D) showed a significant linear correlation with the increase in tissue water content. Histologically, nerve fibers were dissociated and the extracellular space was markedly enlarged with protein-rich fluid. These result showed that the different slopes and intercepts of the water content--Trace(D) correlation lines for different subtype of brain edema, which reflect different ultrastructural localization of water, should be taken into account when evaluating brain edema using Trace(D) mapping.