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Biomedical subjects

Hiroo Ikehira

Publications and source records attributed to Hiroo Ikehira.

17 recordsLinked to original sources

In vivo mapping of substance P receptors in brains of laboratory animals by high-resolution imaging systems.

Neurotransmission mediated by substance P (SP) and NK(1) receptor has been implicated in the pathophysiology of analgesia, emesis and diverse neuropsychiatric conditions including depression and anxiety disorder. Several lines of clinical trials using NK(1) receptor antagonists have been conducted to date, and the efficiency of preclinical assessments for proof of concept and dose optimization could be greatly increased by configuring an in vivo analytical system that permits quantitative mapping of NK(1) receptors in the brains of small-size laboratory animals expressing "human-like" NK(1) receptors. Hence, we investigated the applicability of experimental animals, ranging from rodents to primates, to positron emission tomographic (PET) measurements with [(18)F]fluoroethyl-SPA-RQ, a modification of a recently established radioligand for NK(1) receptors. A pharmacokinetic assay could be performed for a rhesus monkey in an awake condition, which allows the circumvention of influences of anesthesia on SP neurotransmission. Coregistration of PET and magnetic resonance images acquired by small-animal-dedicated devices enabled detailed localization of NK(1) receptors in the gerbil and marmoset brains. The present study also revealed the potentials of SDZ NKT 343 as an antagonist for central NK(1) receptors. In conjunction with additional in vitro and ex vivo autoradiographic observations, our in vivo results have demonstrated a similarity in the binding pattern among the animals examined, justifying cross-species extrapolation of PET findings on the SP-NK(1) pathway.

Animals↗

Age-related degeneration of corpus callosum measured with diffusion tensor imaging.

The corpus callosum is the major commissure connecting the cerebral hemispheres, and there is evidence of its change with aging. The sub-regions of the corpus callosum (genu, rostral body, anterior midbody, posterior midbody, isthmus, splenium) respectively comprise fibers connecting heteromodal- and unimodal-associated cortical regions, and it is known that abnormalities of the corpus callosum are correlated with abnormalities in cognition and behavior. Yet, little is known about changes in the tissue characteristics of its sub-regions. We assessed age-related changes in fractional anisotropy and mean diffusivity in the sub-regions of the corpus callosum using diffusion tensor imaging. We studied 42 healthy right-handed individuals aged 21-73 years. There were no significant interactions of sex x region. Age has significant negative correlation with fractional anisotropy in the genu (P < 0.001), rostral body (P < 0.001), and isthmus (P = 0.005). Fractional anisotropy of the anterior midbody was correlated negatively with age at a trend level (P = 0.022). Age was significantly positively correlated with mean diffusivity in the genu (P = 0.001), rostral body (P = 0.002), anterior midbody (P = 0.001), and isthmus (P = 0.001). Age-related changes were detected in the sub-regions where their projection areas are thought to be vulnerable to normal aging. This suggested that fractional anisotropy and mean diffusivity values of the corpus callosum sub-regions could serve as markers of disturbance across the respective projection areas.

Adult↗

Delayed gadolinium-enhanced MR to determine glycosaminoglycan concentration in reparative cartilage after autologous chondrocyte implantation: preliminary results.

PURPOSE: To prospectively evaluate delayed gadolinium-enhanced magnetic resonance (MR) imaging of cartilage for assessment of glycosaminoglycan (GAG) concentration in reparative cartilage after autologous chondrocyte implantation (ACI). MATERIALS AND METHODS: The study was approved by the ethics review committee of the National Institute of Radiological Sciences, and informed consent was obtained from all patients. The study group comprised nine knees of nine patients (six male, three female; mean age at ACI, 21.2 years +/- 7.5 [standard deviation]; age range, 13-35 years) who had undergone ACI and second-look arthroscopy with biopsy. MR imaging was performed at 1.5 T before and after intravenous injection of anionic gadopentetate dimeglumine. The precontrast R1 (R1(pre)), postcontrast R1 (R1(post)), and difference between R1(pre) and R1(post) (DeltaR1) were measured in reparative cartilage and normal cartilage. GAG concentrations in cartilage biopsy specimens were measured by using high-performance liquid chromatography. To evaluate delayed gadolinium-enhanced MR imaging of cartilage for assessment of GAG concentration, the authors defined the relative R1(pre), relative R1(post), and relative DeltaR1 (ie, R1(pre), R1(post), or DeltaR1, respectively, in reparative cartilage divided by that in normal cartilage) and the relative GAG concentration (ie, GAG concentration in reparative cartilage divided by that in normal cartilage). They then examined the relationships between relative R1(pre), relative R1(post), relative DeltaR1, and relative GAG by using correlation analysis. RESULTS: A significant correlation between relative DeltaR1 and relative GAG concentration (r = 0.818, P < .05) was observed. However, no significant correlation between relative R1(pre) and relative GAG concentration (r = 0.010, P = .983) or between relative R1(post) and relative GAG concentration (r = 0.660, P = .106) was observed. CONCLUSION: Study results indicate that pre- and postcontrast imaging is necessary for delayed gadolinium-enhanced MR imaging evaluation of reparative cartilage after ACI.

Adolescent↗

Quantitative magnetic resonance spectroscopy of schizophrenia: relationship between decreased N-acetylaspartate and frontal lobe dysfunction.

Numerous studies using proton magnetic resonance spectroscopy (1H-MRS) have detected signal changes in schizophrenia. However, most studies investigated relative concentrations such as N-acetylaspartate/creatine plus phosphocreatine (NAA/Cre) and choline-containing compounds/creatine plus phosphocreatine (Cho/Cre), and individual metabolite concentrations have not been clarified. Using absolute quantification measurement of 1H-MRS, the aim of the present paper was to demonstrate the changes in metabolite concentrations in the frontal lobe of patients with chronic schizophrenia. The 1H-MRS was performed in the left frontal lobe in 14 patients with schizophrenia and in 13 healthy comparison subjects. Individual MRS peak concentration was quantified based on a frequency-domain fitting program: LCModel. The scores on the Positive and Negative Symptoms Scale and Wisconsin Card Sorting Test were used for clinical assessment. The NAA concentration was reduced in schizophrenic patients (average, 7.94 mmol/L, t=2.28, P<0.05) compared with healthy subjects (average=8.45 mmol/L) while choline, creatine or NAA/Cre ratio did not show any differences. The reduction in NAA concentration had a significant correlation with the severity of negative symptoms (r=-0.536, P<0.05) and poor performance in Wisconsin Card Sorting Test (r=-0.544, P<0.05). Using quantitative MRS, decreased NAA concentration was confirmed in the left frontal lobe of schizophrenic patients and was demonstrated to be correlated with negative symptoms and cognitive dysfunction in schizophrenia.

Adult↗

Phosphorous-31 magnetic resonance spectroscopy of cervical cancer using transvaginal surface coil.

We developed a new transvaginal coil tuned for phosphorous-31 and measured its magnetic resonance spectroscopy ((31)P MRS) of uterine cervical cancer. In a 50-year-old woman with uterine cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stage IIIb), (31)P MRS with the new coil clearly differentiated the low intensity of phosphocreatinine (PCr) and high intensity of phosphomonoester (PME) in tumor from those in muscle. Results suggests that this method will be useful for assessing uterine cervical cancer.

Carcinoma, Squamous Cell↗

Optimizing T2-weighted magnetic resonance sequences for surface coil microimaging of the eye with regard to lid, eyeball and head moving artifacts.

PURPOSE: To acquire high-resolution magnetic resonance (MR) images, we developed a new blinking artifact reduced pulse (BARP) sequence with a surface coil specialized for microscopic imaging (47 mm in diameter). MATERIALS AND METHODS: To reduce eye movement, we ascertained that the subjects' eyes were kept open and fixated to the target in the 1.5-T MR gantry. To reduce motion artifacts from blinking, we inserted rest periods for blinking (1.5 s within every 5 s) during MR scanning (T2-weighted fast spin echo; repetition time, 5 s; echo time, 100 ms; echo train, 11; matrix, 256 x 128; field of view, 5 cm; 1-mm thickness x 30 slices). Three scans (100 s x 3) were performed for each normal subject, and they were added together after automatic adjustment for location to reduce quality loss caused by head motion. RESULTS: T2-weighted MR images were acquired with a high resolution and a high signal-to-noise ratio. Motion artifacts were reduced with BARP, as compared with those with random blinking. Intraocular structures such as the iris and ciliary muscles were clearly visualized. Because the whole eye can be covered with a 1-mm thickness by this method, three-dimensional maps can easily be generated from the obtained images. CONCLUSION: The application of BARP with a surface coil of the human eye might become a useful and widely adopted procedure for MR microimaging.

Algorithms↗

Functional network in the prefrontal cortex during episodic memory retrieval.

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.

Adult↗

Development of high-radiation-sensitive polymer gel for magnetic resonance imaging in three-dimensional dosimetry.

We developed a high radiation sensitive polymer gel by modifying the amounts of the gel components and the temperature for the gel preparation. We evaluated its relaxation time linearity against dose and compared the measured dose distribution with the calculated one. For the relaxation time-dose linearity, irradiations were carried out with a linear accelerator using 6 MV photons and doses ranging from 0-5.0 Gy. The relationship between dose and R(2) value (reciprocal of T(2) relaxation time) was measured and it had good linearity over a wide range (0.3-5 Gy). The measured dose distributions were in good agreement with calculated ones. Since the present gel has higher sensitivity and it is synthesized more easily at lower cost than conventional polymer gels, we expect to see improved three-dimensional (3D) dosimetry using it.

Dose-Response Relationship, Radiation↗

Metabolic activity in skeletal muscles of patients with non-hypoxaemic chronic obstructive pulmonary disease studied by 31P-magnetic resonance spectroscopy.

OBJECTIVE: An alteration of high energy phosphate metabolism in muscles may contribute to exercise intolerance. The objective of this study was to clarify the changes in high energy phosphate metabolites in muscles during exercise in patients with non-hypoxaemic chronic obstructive pulmonary disease (COPD), which influences the impairment of muscle metabolism. METHODOLOGY: Calf muscle energy metabolism was studied in eight stable non-hypoxaemic COPD patients and eight control subjects, using 31P-magnetic resonance spectroscopy (MRS). MRS spectra were acquired at rest, during exercise at two levels of intensity, and during recovery. The control subjects exercised under both normoxic and hypoxic conditions. The intensity of exercise was standardized by the maximal isometric voluntary contraction (MVC) of the calf muscle and the cross-sectional area (CSA) of calf muscle. RESULTS: MVC and CSA were lower in COPD patients. No significant differences in intracellular pH, inorganic phosphate/phosphocreatine ratio or percentage recovery in inorganic phosphate/phosphocreatine ratio were observed between the two groups in muscles at rest, during exercise or during recovery. CONCLUSIONS: Muscle metabolites, during exercise standardized by muscle CSA and MVC, did not differ between non-hypoxaemic COPD patients and control subjects. MVC, CSA or both, are assumed to be closely related to muscle metabolism, as no difference in high energy phosphate metabolites was observed for COPD patients compared to control subjects when the load was standardized for MVC and CSA. This suggests that high energy metabolites are consumed to a similar extent in the same muscle volume in non-hypoxaemic COPD patients and control subjects.

Aged↗

Time course evaluation of reparative cartilage with MR imaging after autologous chondrocyte implantation.

The aim of this study was to evaluate the qualitative change in reparative cartilage after autologous chondrocyte implantation (ACI). Ten knees of 10 patients were studied. The signal intensities of reparative and normal cartilage were evaluated by fat-suppressed three-dimensional spoiled-gradient recalled (FS 3D-SPGR) MR imaging. The signal intensity (SI) index (signal intensity of reparative cartilage divided by that of normal cartilage) was defined and the change in SI index was investigated. Histological and biochemical evaluation was done at the second look arthroscopy. The SI index was at its lowest level immediately after ACI and increased with time to 9 months thereafter. After 9-12 months, the SI index settled to almost level and was maintained at that value for at least 2-3 years postoperatively. The average of the SI indexes after 12 months to the last examination was 74.2 +/- 4.6 (range 64.2-82.8), which means signal intensity of reparative cartilage was maintained at a value lower than that of normal cartilage. The total ICRS score was 11.6 +/- 2.3 points (mean +/- SD). The GAG concentration was 107.9 +/- 17.0 microg/mg (mean +/- SD) in normal cartilage and 65.9 +/- 9.4 microg/mg in reparative cartilage. The quality of reparative cartilage as hyaline cartilage was inferior to that of normal cartilage. In the present study, the time course change in the SI index indicates that the major maturation process of implanted chondrocytes neared completion in 9-12 months. Minor changes, such as matrix remodeling with reorganization of the collagen fibers in reparative cartilage, may continue, but an almost identical condition seemed to be maintained during the first 2-3 years of follow-up. SI index does not always reflect all properties of reparative cartilage but may be a useful parameter for noninvasive evaluation.

Adolescent↗

The development of a three-dimensional T1 image calculation program in proportion to the DICOM data of any marketing clinical MRI systems.

Contrast media such as gadolinium-diethlene-triamine pentaacetic acid (Gd-DTPA) is used for MRI. Recently there have been some reports about diagnosis using contrast media for the MRI T(1) image for the quantitative evaluation of articular cartilage degeneration. This may be a useful method to evaluate the lesion of the articular cartilage or to confirm therapeutic progress. Whether or not contrast is used, the use of the calculated T(1) image is effective for the quantitative evaluation of the degeneration of knee joint cartilage. However, our system copes with the format of every MRI image even if software of the calculated T(1) image isn't often prepared in the commercial MRI device. So, we developed general purpose image data processing software that can be processed on the preexisting three-dimensional image data processing system.

Cartilage, Articular↗

Neural damage due to temporal lobe epilepsy: dual-nuclei (proton and phosphorus) magnetic resonance spectroscopy study.

The aim of this study was to evaluate the usefulness of proton and phosphorus (1H and 31P) magnetic resonance spectroscopy (MRS) for temporal lobe epilepsy (TLE) patients, and to evaluate neural damage and metabolite dysfunction in the TLE patient brain. We performed 1H and 31P MRS of medial temporal lobes (MTL) in the same TLE patients (n = 14) with a relatively wide range of severity from almost seizure-free to intractable, and calculated the ratio of N-acetylasparate to choline-containing compounds and creatine + phosphocreatine (NAA/Cho + Cr) in 1H MRS and inorganic phosphate to all main peaks (%Pi) in 31P MRS. There was no significant correlation between NAA/(Cho + Cr) and %Pi in each side (ipsilateral, r = -0.20; contralateral, r =-0.19). The values of NAA/(Cho + Cr) showed a significant difference between ipsilateral and contralateral MTLs to the focus of TLE patients (P < 0.01, paired t-test). Although %Pi also had a tendency to show the laterality of TLE, there was no significance. Ipsilateral (r = -0.90, P < 0.0001) and contralateral (r = -0.70, P < 0.005) NAA/(Cho + Cr) decreases and contralateral %Pi increase (r = 0.81, P < 0.001) had significant correlation with seizure frequency. 1H MRS provides more important information concerning neuronal dysfunction in MTL of TLE patients than 31P MRS.

Adult↗

Changes in the pharmacokinetics of Gd-DTPA in experimental tumors after charged particle radiation: comparison with gamma-ray radiation.

We performed dynamic MRI to reveal the characteristic gadopentetate dimeglumine (Gd-DTPA) uptake in carbon-ion irradiated tumor and compare it with photon irradiation. Fibrosarcomas in C3H mice legs were irradiated with either 16 Gy of carbon ions (74 keV/mm) or an equivalent dose (30 Gy) of Cs-137 gamma-rays. Dynamic MRI was performed 1 or 6 days after irradiation when the tumors showed an initial growth delay or incipient regrowth, respectively. The enhancement pattern was visualized by mapping the maximum enhanced time (Tmax), relative signal intensity maximum (SImax), and time delay of starting enhancement (Td). Significantly larger Tmax and Td values were observed in the tumors 1 day after carbon-ion irradiation than in the nonradiated tumors (No-R) and tumors 1 day after gamma-ray irradiation. Among the selected pixels in the tumors 6 days after carbon irradiation, 77% had Tmax values of less than 120 sec, significantly more than in the No-R group. The Tmax maps for the tumors irradiated with gamma-rays showed a similar tendency to the carbon-irradiated ones, and only a significant difference was obtained between tumors 1 and 6 days after irradiation. Tmax and Td in the carbon-ion irradiated tumors were different from those in the gamma-ray-irradiated tumors. These treatment-specific kinetics may be useful in predicting the therapeutic efficacy of carbon-ion treatment.

Animals↗

Histologic characteristics of normal perivascular spaces along the optic tract: new pathogenetic mechanism for edema in tumors in the pituitary region.

BACKGROUND AND PURPOSE: Perivascular (PV) spaces are known to distend and cause edema along the optic tract (OT) in pituitary-region tumors. Interstitial fluid may be retained in PV spaces when tumors block their drainage outlets to subarachnoid spaces. However, these spaces and their outlets have not been anatomically elucidated. Our purpose was to evaluate how often large PV spaces are present along the OT and demonstrate their superficial communication points to adjacent subarachnoid spaces. METHODS: We examined serial histologic sections of 10 hemispheric blocks obtained from cadavers without cerebral abnormality. RESULTS: Large PV spaces, 0.5-1.5 mm in maximum height, were always present along the middle portion of the OT. Perforation points of the largest spaces were noted at the medial sulcus of the OT in seven hemispheres and through the OT in three. CONCLUSION: Large PV spaces are present along the middle portion of the OT. Their communication point to adjacent subarachnoid spaces was histologically demonstrated. The locations and variations of the outlet of large PV spaces explain the clinical features of edemas; these findings anatomically support the hypothesis that blockage of the outlets to subarachnoid spaces may play a role in distending the PV spaces and in causing edema in pituitary-region tumors. Only MR imaging has revealed this change; further pathologic investigations are awaited.

Aged↗

Development of a dielectric equivalent gel for better impedance matching for human skin.

It would be useful to develop a tissue equivalent gel to improve the uniformity of the electromagnetic field in the human body, and for making a tissue equivalent dielectric human phantom. In this study, solid type, water based gelatin-honey gels were developed which have the electrical characteristics of skin tissue. It was demonstrated that a stable and homogeneous gel, with a relative dielectric constant epsilon ' chosen from desired ranges found in skin, can be made for 200-400 MHz.

Biomimetic Materials↗

Measurement of the electrical properties of human skin and the variation among subjects with certain skin conditions.

In this study the dielectric properties are reported for human skin tissues over the frequency range 1-450 MHz at 36 degrees C. Healthy volunteers, collagen disease patients and dialysis patients are studied in order to investigate, primarily, the variability among (1) different regions of one individual, (2) the same region among different individuals and (3) skin conditions due to diseases. Considerable differences exist among the skin dielectric properties obtained from different regions of one individual body. Although region dependence is observed, larger variability is found even in the same skin region among individuals.

Collagen↗

19F-magnetic resonance spectroscopy and chemical shift imaging for schizophrenic patients using haloperidol decanoate.

Haloperidol decanoate is widely used in the maintenance treatment of schizophrenia and other psychotic disorders, but knowledge concerning its pharmacokinetics at the injected region is very limited. Because the chemical structure of haloperidol contains fluorine, in vivo 19F-magnetic resonance (MR) spectroscopy (repetition time (TR) = 1 s) and chemical shift imaging (CSI; TR = 1 s, pixel size = 15 x 15 mm) were performed in schizophrenic patients who were treated with haloperidol decanoate (three men and one woman) to measure its diachronic change at the injection point and visualize its local distribution after intramuscular injection. 19F signals (T1 time = 365 ms) were obtained at the haloperidol decanoate-injected region. The decrease rate of the signal-to-noise ratio (SNR) by 19F-MR spectroscopy seemed large in comparison with that of the plasma haloperidol concentration. The distribution was clearly visualized by 19F-CSI for a few days after the injection, but after 1 week could no longer be seen. Although the slow-release characteristics of depot neuroleptics have been explained by the slow diffusion of esterified neuroleptics from the oil vehicle, this result may suggest that there are other mechanisms involved in maintaining the plasma haloperidol concentration. In vivo 19F-MR spectroscopy and CSI are potentially applicable for the pharmacokinetic analysis of haloperidol and other drugs containing fluorine in their structure.

Adult↗