Inhibitory Effects of P2Y12 Receptor Antagonist on PAR1- and PAR4-AP-Induced Platelet Aggregation in Patients with Stroke or TIA.

OBJECTIVES: The inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-activating peptide (AP)-induced platelet aggregation have not been fully elucidated. The present study aimed to investigate the inhibitory effects of P2Y12 receptor antagonist on PAR1- and PAR4-AP-induced platelet aggregation using platelet-rich plasma (PRP) from individuals including patients with stroke or transient ischemic attack (TIA). MATERIALS AND METHODS: PRP was given to 10 healthy individuals pretreated in vitro with cangrelor, then stimulated with adenosine diphosphate (ADP), PAR4-AP, or PAR1-AP. Moreover, 20 patients were enrolled from 148 consecutive patients with acute ischemic stroke or TIA admitted to our institute between December 2017 and April 2019. PRP obtained from each patient before and >7 days after initiation of clopidogrel was similarly stimulated with these agonists. Platelet aggregation was measured using an automatic coagulation analyzer in all participants. RESULTS: In healthy individuals, ADP- and PAR4-AP-induced platelet aggregations were significantly inhibited depending on the cangrelor concentration in vitro, while PAR1-AP-induced platelet aggregation was slightly inhibited. In patients with stroke or TIA, clopidogrel inhibited ADP-induced platelet aggregation at all concentrations, and significantly inhibited PAR4-AP-induced platelet aggregation at 50 µmol/L of PAR4-AP (p<0.05), especially in 5 patients who showed high reactivity to PAR4-AP. PAR1-AP-induced platelet aggregation was also slightly inhibited. CONCLUSIONS: We showed significant inhibitory effects on PAR4-AP-induced platelet aggregation by clopidogrel in patients with stroke or TIA who had high reactivity to PAR4-AP.

Thrombin-induced platelet aggregation -effect of dabigatran using automated platelet aggregometry.

Dabigatran, a direct oral thrombin inhibitor, has two therapeutic effects: anticoagulation; and antiplatelet activity. In the clinical field, evaluation of the effect of dabigatran on thrombin-induced platelet aggregation is difficult because of fibrin clot formation and platelet aggregation. The aim of this study was to establish a new platelet aggregation method and to investigate the effects of dabigatran on thrombin-induced platelet aggregation. Platelet aggregation with thrombin was performed with automated light transmission aggregometry (CS2400; Sysmex, Kobe, Japan) in 40 healthy subjects. Thrombin-induced platelet aggregation was performed using thrombin and platelet-rich plasma (PRP), and thrombin-induced fibrin polymerization was inhibited by adding the peptide Gly-Pro-Arg-Pro (GPRP). The effect of dabigatran was then evaluated using the above method. Thrombin at < 0.2 U/mL did not induce platelet aggregation in most normal subjects. Median maximum aggregation percent (MA%) (25th-75th percentile) with 0.5 and 1.0 U/mL of thrombin was 87.0% (79.3-90.8%), and 90.2% (86.5-92.2%), respectively. The anti-platelet effects of dabigatran were then evaluated with these concentrations of thrombin. Dabigatran (final concentration, 2.5-1000 nM) inhibited platelet aggregation by 0.2-1.0 U/mL of thrombin in a concentration-dependent manner in vitro. Dabigatran showed potent inhibitory effects against platelet aggregation induced by 0.5 and 1.0 U/mL thrombin with half maximal inhibitory concentrations of 10.5 and 40.4 nM, respectively. A standard for thrombin-induced platelet aggregation was developed using the CS2400 in healthy subjects, and dabigatran was confirmed to inhibit thrombin-induced platelet aggregation in vitro with PRP.

T1-Weighted Magnetic Resonance Carotid Plaque Imaging: a Comparison between Conventional and Fast Spin-Echo Techniques.

BACKGROUND: Magnetic resonance imaging is widely used to evaluate the intraplaque components of the cervical carotid artery. The non-gated T1-weighted spin-echo (SE) technique has been reported to have an excellent ability for discriminating stable and unstable plaques. However, the diagnostic performance of various SE-based techniques remains unclear. Hence, we compared plaque signals obtained by 3 kinds of SE-based methods with histological findings. METHODS: We prospectively examined 40 patients who underwent carotid endarterectomy by using 1.5-T scanners and obtained 2-dimensional (2D) conventional spin-echo (CSE), 2D fast spin-echo (FSE), and 3-dimensional (3D)-FSE images with identical repetition times. We calculated contrast ratios (CRs) of the plaques against adjacent muscles and compared these values with the pathological classification of the specimens. RESULTS: The CRs of type VII-VIII (calcific/fibrous), IV-V (lipid-rich/necrotic), and VI (complex/hemorrhagic) plaques were significantly different between all the methods (P <.001) and were discriminated from each other at sensitivities of 83%-100% and specificities of 94%-100%. The CRs of type IV-V plaques significantly differed between the methods (low to high, 2D-FSE, 2D-CSE, and 3D-FSE; P <.05); those of the type VI plaques were significantly lower with the 2D-FSE method than with the other methods (P <.01). CONCLUSIONS: The SE-based T1-weighted images can readily discriminate plaque characteristics with high sensitivities and specificities, although the signal intensity of unstable plaques was significantly high on the 3D-FSE images and significantly low on the 2D-FSE images.

Comparison of Three-Dimensional T1-Weighted Magnetic Resonance and Contrast-Enhanced Ultrasound Plaque Images for Severe Stenosis of the Cervical Carotid Artery.

BACKGROUND AND PURPOSE: Magnetic resonance (MR) and contrast-enhanced ultrasound assess characteristics and neovascularization, respectively, of the carotid plaque. The purpose of the present study was to clarify how findings of contrast-enhanced ultrasound plaque imaging are related to those of 3-dimensional (3D) fast spin echo (FSE) T1-weighted MR plaque imaging (WI) in severe stenosis (≥70%) of the cervical carotid artery. METHODS: Fifty-three patients underwent 3D FSE T1-WI and contrast-enhanced ultrasound. For each patient, the averaged contrast ratio on MR (CRMR) was calculated by dividing the averaged internal carotid artery plaque signal intensity by the sternocleidomastoid muscle signal intensity; maximally enhanced intensities on the intraplaque and lumen time-intensity curves were obtained from contrast-enhanced ultrasound data, and the ratio of the maximal intensity of the intraplaque curve to that of the lumen curve was calculated and defined as contrast effect (CEUS). RESULTS: A linear correlation (r = .702; P <.0001) was observed between CRMR and CEUS. Receiver operating characteristic curve analyses to evaluate the ability of the CEUS to differentiate each category of CRMR from the other 2 categories showed that the sensitivity was significantly lower for category II (1.30 ≤ CRMR ≤ 1.60) than for category I (CRMR < 1.30) or III (1.60 < CRMR). The CEUS was lower in plaques with higher CRMR than in those with lower CRMR in a subgroup of category III (P = .0196). CONCLUSION: Findings of contrast-enhanced ultrasound plaque imaging are related to those of 3D FSE T1-WI MR plaque imaging according to the life history of arterial plaque and its neovascularization.

Preoperative 3D FSE T1-Weighted MR Plaque Imaging for Severely Stenotic Cervical ICA: Accuracy of Predicting Emboli during Carotid Endarterectomy.

The aim of the present study was to determine whether preoperative three-dimensional (3D) fast spin-echo (FSE) T1-weighted magnetic resonance (MR) plaque imaging for severely stenotic cervical carotid arteries could accurately predict the development of artery-to-artery emboli during exposure of the carotid arteries in carotid endarterectomy (CEA). Seventy-five patients underwent preoperative MR plaque imaging and CEA under transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. On reformatted axial MR image slices showing the maximum plaque occupation rate (POR) and maximum plaque intensity for each patient, the contrast ratio (CR) was calculated by dividing the internal carotid artery plaque signal intensity by the sternocleidomastoid muscle signal intensity. For all patients, the area under the receiver operating characteristic curve (AUC)-used to discriminate between the presence and absence of microembolic signals-was significantly greater for the CR on the axial image with maximum plaque intensity (CRmax intensity) (0.941) than for that with the maximum POR (0.885) (p < 0.05). For 32 patients in whom both the maximum POR and the maximum plaque density were identified, the AUCs for the CR were 1.000. Preoperative 3D FSE T1-weighted MR plaque imaging accurately predicts the development of artery-to-artery emboli during exposure of the carotid arteries in CEA.

Intracranial Plaque Characterization in Patients with Acute Ischemic Stroke Using Pre- and Post-Contrast Three-Dimensional Magnetic Resonance Vessel Wall Imaging.

BACKGROUND: Magnetic resonance vessel wall imaging (VWI) techniques have been developed to assess atherosclerotic plaques in intracranial arteries, which are a cardinal cause of ischemic stroke. However, the clinical roles of plaque-related vulnerability and inflammation remain unclear. Hence, we evaluated plaque characteristics using VWI of the proximal middle cerebral artery (M1) in patients with acute ischemic stroke. METHODS: We prospectively examined 30 consecutive patients with acute noncardioembolic stroke in the M1 territory using pre-/postcontrast T1-weighted (T1W) three-dimensional (3D) VWI with a 3-Tesla scanner. The contrast ratio (CR) and contrast enhancement of the plaques were measured bilaterally at M1. RESULTS: Plaques were identified in the bilateral M1s of all patients, and no substantial stenosis existed. The M1 plaque CRs ipsilateral to the infarct (46.7%-67.9%) were significantly higher than the plaque CRs on the contralateral side (34.3%-69.4%), particularly in patients with lacunar infarcts (P <.01). In contrast, the occurrence of plaque enhancement was not different between the ipsilateral (20.0%) and contralateral (16.7%) sides. Further, the CRs in the nonlacunar group were significantly higher than the CRs in the lacunar group (P <.05), whereas enhanced plaques tended to be more frequent in the nonlacunar group, but this difference was not significant (P = .09). CONCLUSIONS: T1W 3D-VWI revealed that the signal intensity of M1 plaques was significantly higher in the affected side and in nonlacunar-type infarcts of patients with acute stroke, suggesting that unstable plaques in the M1 can cause stroke events presumably due to atherothrombotic mechanisms.

Carotid plaque characteristics on magnetic resonance plaque imaging following long-term cilostazol therapy.

BACKGROUND: Cilostazol is an antiplatelet agent that can induce the regression of atherosclerosis. However, its long-term effects on plaque involution of the cervical carotid arteries remain unknown. Thus, we aimed to evaluate the effect of long-term cilostazol administration on carotid plaques using quantitative magnetic resonance (MR) plaque imaging. METHODS: Sixteen consecutive patients with carotid stenosis were examined using T1-weighted MR plaque imaging at baseline, 6 months, and 12 months after initiation of 200 mg per day of cilostazol. We calculated the contrast ratio of the carotid plaque against the sternocleidomastoid muscle and percent areas of the intraplaque fibrous tissue, lipid/necrosis, and hemorrhage components using automated software. We also measured the volume and echogenicity of the plaques using 3-dimensional ultrasonography. RESULTS: The contrast ratio of the carotid plaque significantly decreased during the cilostazol administration (median 1.07, 1.04, and 1.00 at baseline, 6 months, and 12 months, respectively; P = .03). Furthermore, the area of the fibrous components significantly increased (73.9%, 80.3%, and 85.7%, respectively; P = .03) and that of the lipid/necrotic components significantly decreased (25.2%, 19.2%, and 14.3%, respectively; P = .04). There were no substantial changes in plaque volume or echogenicity on ultrasonography. CONCLUSIONS: Signal alterations on MR plaque imaging indicated the increase of fibrous components and the decrease of lipid/necrotic components in the carotid plaque during the cilostazol therapy.

Detection of vessel wall lesions in spontaneous symptomatic vertebrobasilar artery dissection using T1-weighted 3-dimensional imaging.

BACKGROUND: Spontaneous intracranial vertebrobasilar artery dissection (iVBD) is a cause of ischemic stroke and subarachnoid hemorrhage in young adults that can be detected noninvasively by using multisequence magnetic resonance imaging (MRI). However, MRI findings are sometimes difficult to interpret, and its accuracy tends to be suboptimal, especially during the acute period. Therefore, we investigated whether 3-dimensional (3D) vessel wall imaging (VWI) technique could readily detect iVBD lesions in acute phase patients. METHODS: Sixteen consecutive patients with acute ischemic stroke caused by iVBD were prospectively examined with a 1.5-T magnetic resonance scanner. T1-weighted (T1W) 3D-VWI was obtained using a flow-sensitized 3D fast spin-echo technique. In addition, multisequence MRI comprising magnetic resonance angiography (MRA), basiparallel anatomical scanning (BPAS), and axial T1W imaging (T1WI) were also examined. Presence of luminal stenosis, aneurysmal dilatation, intramural high signal, and intimal flap/double lumen of the vertebral and basilar arteries were visually assessed using each technique. RESULTS: On 3D-VWI, luminal stenosis, aneurysmal dilatation, intramural high signal, and intimal flap were observed in 16 (100%), 11 (68.8%), 16 (100%), and 1 (6.3%) patients, respectively. In contrast, on conventional techniques, these findings were observed in 15 (93.8%, MRA with BPAS), 12 (75.0%, MRA with BPAS), 12 (75.0%, T1WI), and 12 (75.0%, MRA) patients, respectively. CONCLUSIONS: The T1W 3D-VWI can directly visualize vessel wall iVBD lesions during the acute period of stroke compared with multisequence MRI.

Evaluating middle cerebral artery atherosclerotic lesions in acute ischemic stroke using magnetic resonance T1-weighted 3-dimensional vessel wall imaging.

BACKGROUND: Atherosclerotic lesions in intracranial arteries are a leading cause of ischemic stroke. Magnetic resonance angiography (MRA) is often used to assess atherosclerotic changes by detecting luminal narrowing, whereas it cannot directly visualize atherosclerotic lesions. Here, we used a 3-dimensional vessel wall imaging (3D-VWI) technique to evaluate intracranial arterial wall changes in acute stroke. METHODS: Eighteen consecutive patients with acute noncardioembolic stroke in the middle cerebral artery (MCA) territory who were prospectively examined with a 1.5-T magnetic resonance scanner were studied. T1-weighted (T1-W) 3D-VWI was obtained using a flow-sensitized 3D fast-spin echo technique. Wall thickening of MCA that suggests atherosclerotic plaques was visually evaluated and the contrast ratio (CR) of signal intensity of the lesions to that of the corpus callosum was calculated and compared with stenotic changes by MRA. RESULTS: Wall thickenings of the MCA ipsilateral and contralateral to the lesion were observed in almost all patients on 3D-VWI (94.4% and 94.4%, respectively), whereas MRA showed stenotic changes of 50% only in 1 patient (5.9%; P < .001). The CR of the thickened wall in the ipsilateral MCA was significantly higher than that in the contralateral MCA (median, .53 and .45, respectively; P = .028), suggesting of unstable plaques consisting of hemorrhage or lipid. CONCLUSIONS: The T1-W 3D-VWI can provide direct visualization of atherosclerotic lesions of the intracranial arteries in stroke patients, and it can detect signal change suggestive of unstable plaque.

Carotid plaque signal differences among four kinds of T1-weighted magnetic resonance imaging techniques: a histopathological correlation study.

INTRODUCTION: Several magnetic resonance (MR) imaging techniques are used to examine atherosclerotic plaque of carotid arteries; however, the best technique for visualizing intraplaque characteristics has yet to be determined. Here, we directly compared four kinds of T1-weighted (T1W) imaging techniques with pathological findings in patients with carotid stenosis. METHODS: A total of 31 patients who were candidates for carotid endarterectomy were prospectively examined using a 1.5-T MRI scanner, which produced four kinds of T1W images, including non-gated spin echo (SE), cardiac-gated black-blood (BB) fast-SE (FSE), magnetization-prepared rapid acquisition with gradient echo (MPRAGE), and source image of three-dimensional time-of-flight MR angiography (SI-MRA). The signal intensity of the carotid plaque was manually measured, and the contrast ratio (CR) against the adjacent muscle was calculated. CRs from the four imaging techniques were compared to each other and correlated with histopathological specimens. RESULTS: CRs of the carotid plaques mainly containing fibrous tissue, lipid/necrosis, and hemorrhage were significantly different with little overlaps (range: 0.92-1.15, 1.22-1.52, and 1.55-2.30, respectively) on non-gated SE. However, BB-FSE showed remarkable overlaps among the three groups (0.89-1.10, 1.07-1.23, and 1.01-1.42, respectively). MPRAGE could discriminate fibrous plaques from hemorrhagic plaques but not from lipid/necrosis-rich plaques: (0.77-1.07, 1.45-2.43, and 0.85-1.42, respectively). SI-MRA showed the same tendencies (1.01-1.39, 1.45-2.57, and 1.12-1.39, respectively). CONCLUSION: Among T1W MR imaging techniques, non-gated SE images can more accurately characterize intraplaque components in patients who underwent CEA when compared with cardiac-gated BB-FSE, MPRAGE, and SI-MRA images.

Quantitative assessment of changes in carotid plaques during cilostazol administration using three-dimensional ultrasonography and non-gated magnetic resonance plaque imaging.

INTRODUCTION: Cilostazol, an antiplatelet agent, is reported to induce the regression of atherosclerotic changes. However, its effects on carotid plaques are unknown. Hence, we quantitatively investigated the changes that occur within carotid plaques during cilostazol administration using three-dimensional (3D) ultrasonography (US) and non-gated magnetic resonance (MR) plaque imaging. METHODS: We prospectively examined 16 consecutive patients with carotid stenosis. 3D-US and T1-weighted MR plaque imaging were performed at baseline and 6 months after initiating cilostazol therapy (200 mg/day). We measured the volume and grayscale median (GSM) of the plaques from 3D-US data. We also calculated the contrast ratio (CR) of the carotid plaque against the adjacent muscle and areas of the intraplaque components: fibrous tissue, lipid, and hemorrhage components. RESULTS: The plaque volume on US decreased significantly (median at baseline and 6 months, 0.23 and 0.21 cm(3), respectively; p = 0.03). In the group exhibiting a plaque volume reduction of more than 10%, GSM on US increased significantly (24.8 and 71.5, respectively; p = 0.04) and CR on MRI decreased significantly (1.13 and 1.04, respectively; p = 0.02). In this group, in addition, the percent area of the fibrous component on MRI increased significantly (68.6% and 79.4%, respectively; p = 0.02), while those of the lipid and hemorrhagic components decreased (24.9% and 20.5%, respectively; p = 0.12) (1.0% and 0.0%, respectively; p = 0.04). There were no substantial changes in intraplaque characteristics in either US or MRI in the other group. CONCLUSIONS: 3D-US and MR plaque imaging can quantitatively detect changes in the size and composition of carotid plaques during cilostazol therapy.

1H-magnetic resonance spectroscopy indicates damage to cerebral white matter in the subacute phase after CO poisoning.

OBJECTIVE: The authors examined whether (1)H-magnetic resonance spectroscopy (MRS) can identify damage to the centrum semiovale in the subacute phase after CO exposure. METHODS: Subjects comprised 29 adult patients who were treated with hyperbaric oxygenation within a range of 4-95 h (mean 18.7 h) after CO exposure. Subjects were classified into three groups according to clinical behaviours: Group A, patients with transit acute symptoms only; Group P, patients with persistent neurological symptoms; and Group D, patients with 'delayed neuropsychiatric sequelae' occurring after a lucid interval. MRS of bilateral centrum semiovale was performed 2 weeks after CO inhalation for all patients and 13 healthy volunteers. The mean ratios of choline-containing compounds/creatine ((mean)Cho/Cr) and N-acetylaspartate/Cr ((mean)NAA/Cr) for bilateral centrum semiovale were calculated and compared between the three CO groups and controls. Myelin basic protein (MBP) concentration in cerebrospinal fluid was examined at 2 weeks to evaluate the degree of demyelination in patients. RESULTS: MBP concentration was abnormal for almost all patients in Groups P and D, but was not abnormal for any Group A patients. The (mean)Cho/Cr ratios were significantly higher in Groups P and D than in Group A. No significant difference in (mean)NAA/Cr ratio was seen between the three pathological groups and controls. A significant correlation was identified between MBP and (mean)Cho/Cr ratio. CONCLUSIONS: These results suggest that the Cho/Cr ratio in the subacute phase after CO intoxication represents early demyelination in the centrum semiovale, and can predict chronic neurological symptoms.

Evaluating recanalization of relevant lenticulostriate arteries in acute ischemic stroke using high-resolution MRA at 7T.

BACKGROUND: Occluded major intracranial arteries can spontaneously recanalize in patients with acute ischemic stroke mainly due to embolic mechanisms. However, it remains unknown whether recanalization can occur in perforating arteries, such as lenticulostriate arteries. Therefore, in the present study, we assessed changes suggesting recanalization of the lenticulostriate arteries in patients with acute ischemic stroke of the lenticulostriate artery territory using high-resolution magnetic resonance angiography (HR-MRA) at 7T. METHODS: We prospectively examined 39 consecutive patients with acute infarcts confined within the lenticulostriate artery territory. Using a 7T scanner during the acute period and one month thereafter, we evaluated imaging findings indicating the recanalization of the relevant lenticulostriate arteries, following which we examined differences in other imaging findings and clinical characteristics between patients with/without recanalization. RESULTS: HR-MRA findings suggestive of recanalization (i.e. patent lenticulostriate arteries within acute infarct lesions with/without hemorrhagic changes) were observed in 8 (25%) of 32 patients who were eligible for analyses. These findings were detected in three and five patients on the baseline and follow-up images, respectively. The lengths of relevant lenticulostriate arteries on the follow-up MRA were significantly larger in patients with recanalization than in those without (P = 0.01). However, there were no significant differences in the infarct volume or clinical outcomes between the recanalization and non-recanalization groups. CONCLUSION: HR-MRA at 7T revealed that recanalization of the relevant lenticulostriate arteries can occur in patients with acute ischemic stroke confined to the lenticulostriate artery territory.

Influence of PAR-1 in patients with non-valvular atrial fibrillation: The antiplatelet effect of dabigatran.

INTRODUCTION: Dabigatran, a direct thrombin inhibitor, has been widely used in patients with non-valvular atrial fibrillation (NVAF) and is considered to have an antiplatelet effect. However, the mechanisms remain unclear. We evaluated protease-activated receptor-1 (PAR-1) expression and activation by thrombin on platelets from NVAF patients, before and after dabigatran treatment, in addition to the expression of platelet activation marker CD62P. MATERIALS AND METHODS: The study included 18 NVAF patients. We used flow cytometry to measure the binding of PAR-1 monoclonal antibodies (SPAN12 and WEDE15) and the expression of CD62P with and without thrombin stimulation, before, 14 days after, and 28 days after treatment with dabigatran. Coagulation fibrinolysis markers were also measured. RESULTS: PAR-1 expression was significantly lower in NVAF patients than in healthy controls (HC); it was further reduced by thrombin stimulation. CD62P expression was almost absent on the platelets in NVAF patients, but was significantly increased by thrombin stimulation. PAR-1 expression was not significantly different before and after treatment; CD62P expression was inhibited by dabigatran. The levels of coagulation markers were significantly higher in NVAF patients than in HC, and decreased after treatment. CONCLUSIONS: Lower expression of PAR-1 in NVAF patients resulted from the cleavage of PAR-1 on some platelets, by exposure to small amounts of thrombin in vivo. The therapeutic effect of dabigatran in NVAF patients was demonstrated by inhibition of CD62P expression on the platelet upon thrombin stimulation in vitro. Our results indicate that dabigatran may reveal antithrombotic activity with antiplatelet and anticoagulant effects.

Visual discrimination among patients with depression and schizophrenia and healthy individuals using semiquantitative color-coded fast spin-echo T1-weighted magnetic resonance imaging.

INTRODUCTION: Fast spin-echo (FSE) T1-weighted (T1W) magnetic resonance imaging (MRI) at 3T, which is sensitive to neuromelanin-related contrast, can quantitatively detect signal alterations in the locus ceruleus (LC) and the substantia nigra pars compacta (SNc) of depressive and schizophrenic patients; however, its qualitative diagnostic performance remains unknown. We investigated whether visual interpretation of semiquantitative color maps can be used for discriminating between depressive and schizophrenic patients and healthy individuals. METHODS: We retrospectively examined 23 patients with major depression, 23 patients with schizophrenia, and 23 age-matched healthy controls by using a FSE-T1W MRI technique. Semiquantitative color maps of sections through the LC and SNc were visually interpreted by nine raters using a continuous confidence rating scale for receiver operating characteristic (ROC) analysis. RESULTS: The area under the ROC curve (Az), which reflects the performance in differentiating between depressive patients and controls, was 0.88, and the sensitivity and specificity at the maximum likelihood were 76% and 83%, respectively. In contrast, the Az value, sensitivity, and specificity values between schizophrenics and controls and between depressives and schizophrenics were 0.66 and 0.69, 42% and 48%, and 82% and 84%, respectively. CONCLUSION: Semiquantitative, color-coded FSE-T1W MRI at 3T can be used for visually differentiating depressive patients from healthy individuals with a substantially high likelihood, but this technique cannot be applied to distinguish schizophrenic patients from the other two groups.

Detection of changes in cerebrospinal fluid space in idiopathic normal pressure hydrocephalus using voxel-based morphometry.

INTRODUCTION: We attempted to detect alterations in the cerebrospinal fluid (CSF) space in patients with idiopathic normal pressure hydrocephalus (iNPH) using voxel-based morphometry (VBM). METHODS: We obtained sagittal volume images of the entire head by three-dimensional T1-weighted magnetic resonance imaging and compared the regional distribution of CSF in 12 patients with iNPH, 14 patients with Alzheimer's disease (AD), and 17 healthy individuals using VBM with automatically extracted CSF objects. RESULTS: VBM demonstrated significant widening at the lateral ventricles and Sylvian fissures and narrowing of the CSF space at the high convexity/midline areas in iNPH patients, compared to the AD patients and healthy controls (p < 0.05, after correction with a false-discovery rate). In addition, the ratio of the CSF volume in the lateral ventricle/Sylvian fissure area to that in the high convexity/midline area in iNPH patients (3.9 +/- 1.2) was remarkably greater than that in AD patients (1.2 +/- 0.3) and controls (0.9 +/- 0.3; one-way ANOVA, p < 0.001; post hoc Tukey's test, p < 0.001); we could discriminate iNPH patients from those in the other two groups without any overlap, when using a cutoff level of 1.9. CONCLUSION: VBM using CSF objects can be used to delineate the characteristic alteration of the CSF space in iNPH patients, which has been evaluated by visual interpretation.

Altered carotid plaque signal among different repetition times on T1-weighted magnetic resonance plaque imaging with self-navigated radial-scan technique.

INTRODUCTION: Magnetic resonance (MR) plaque imaging for carotid arteries is usually performed by using an electrocardiograph (ECG)-gating technique to eliminate pulsation-related artifacts, which can affect the plaque signals because of varied repetition time (TR) among patients. Hence, we investigated whether differences in TR causes signal alterations of the carotid plaque by using a non-gated plaque imaging technique. METHODS: We prospectively examined 19 patients with carotid stenosis by using a T1-weighted self-navigated radial-scan technique with TRs of 500, 700, and 900 ms. The signal intensity of the carotid plaque was measured, and the contrast ratio (CR) relative to the adjacent muscle was calculated. RESULTS: CRs of the carotid plaques were 1.39 +/- 0.39, 1.29 +/- 0.29, and 1.23 +/- 0.24 with TRs of 500, 700, and 900 ms, respectively, and were significantly different. Among the plaques, those with a hyperintensity signal (CR > 1.5) and moderate-intensity signal (CR 1.2-1.5) at 500 ms showed a TR-dependent signal decrease (hyperintensity plaques, 1.82 +/- 0.26; 1.61 +/- 0.19; and 1.48 +/- 0.17; moderate-intensity plaques, 1.33 +/- 0.08; 1.26 +/- 0.08; and 1.19 +/- 0.07), while those with an isointensity signal (CR < 1.2) remained unchanged regardless of TR (0.96 +/- 0.12, 0.96 +/- 0.11, and 0.97 +/- 0.13). CONCLUSION: The signal intensity of the carotid plaque on T1-weighted imaging significantly varies among different TRs and tends to decrease with longer TR. MR plaque imaging with short and constant TR settings that the ECG-gating method cannot realize would be preferable for evaluating plaque characteristics.

An Anatomical Variation in the Cervical Carotid Artery of a Young Stroke Patient.

The cervical carotid artery has been reported to show anatomical variations. We report the case of a young stroke patient with a small right-parietal-lobe infarction whose cervical carotid artery showed anatomical variation. The right internal carotid artery (ICA) originated at the C2 level of the external carotid artery with protrusion at the right carotid bifurcation. The vessel wall of the protrusion showed a high signal intensity on T1-weighted magnetic resonance carotid plaque imaging. The protrusion, considered a remnant of the ICA, possibly caused the stroke due to the formation of thrombi as a result of changes in blood flow and viscosity.

Detecting lenticulostriate artery lesions in patients with acute ischemic stroke using high-resolution MRA at 7 T.

BACKGROUND: Recent advances in high-resolution (HR) magnetic resonance angiography (MRA) using ultrahigh-field systems enable direct visualization of the lenticulostriate arteries (LSAs), which had been hardly achieved by conventional MRA. Hence, by using HR-MRA at 7 T, we attempted to assess occlusive changes in the LSAs in patients with LSA territorial infarcts. METHODS: We prospectively examined 34 consecutive patients with acute ischemic stroke in the LSA territory using a 7 T scanner. We measured the lengths of the relevant LSAs on HR-MRA and the diameters/volume of the infarcts and compared these between the patients with/without occlusive changes in the LSAs. RESULTS: On HR-MRA, occlusion of the LSAs was observed in 19 (59%) of 32 patients who were eligible for the analyses. The curved/straight lengths of the LSAs in the patients with LSA occlusion (23.1-31.1/17.8-24.3 mm) were significantly shorter than in those without apparent LSA occlusion (25.8-39.5/24.0-30.4 mm) ( P = 0.027/0.003). The anteroposterior/superoinferior diameters of the infarcts were significantly larger in the occluded-LSA group (14.5-21.4/14.9-22.2 mm) than in the intact-LSA group (10.9-16.8/10.8-16.2 mm) ( P = 0.041/0.011). In addition, the curved lengths of the relevant LSAs showed significant correlations with the superoinferior diameters of the infarcts ( r = 0.38, P = 0.034). CONCLUSION: Occlusive changes in the LSAs were frequently found in patients with acute ischemic stroke within the LSA territory when using HR-MRA at 7 T and were substantially related to superoinferior extension of the infarcts.

Novel pathogenic XK mutations in McLeod syndrome and interaction between XK protein and chorein.

OBJECTIVE: To identify XK pathologic mutations in 6 patients with suspected McLeod syndrome (MLS) and a possible interaction between the chorea-acanthocytosis (ChAc)- and MLS-responsible proteins: chorein and XK protein. METHODS: Erythrocyte membrane proteins from patients with suspected MLS and patients with ChAc, ChAc mutant carriers, and normal controls were analyzed by XK and chorein immunoblotting. We performed mutation analysis and XK immunoblotting to molecularly diagnose the patients with suspected MLS. Lysates of cultured cells were co-immunoprecipitated with anti-XK and anti-chorein antibodies. RESULTS: All suspected MLS cases were molecularly diagnosed with MLS, and novel mutations were identified. The average onset age was 46.8 ± 8 years, which was older than that of the patients with ChAc. The immunoblot analysis revealed remarkably reduced chorein immunoreactivity in all patients with MLS. The immunoprecipitation analysis indicated a direct or indirect chorein-XK interaction. CONCLUSIONS: In this study, XK pathogenic mutations were identified in all 6 MLS cases, including novel mutations. Chorein immunoreactions were significantly reduced in MLS erythrocyte membranes. In addition, we demonstrated a possible interaction between the chorein and XK protein via molecular analysis. The reduction in chorein expression is similar to that between Kell antigens and XK protein, although the chorein-XK interaction is a possibly noncovalent binding unlike the covalent Kell-XK complex. Our results suggest that reduced chorein levels following lack of XK protein are possibly associated with molecular pathogenesis in MLS.