Importance of Age and Noncontrast-Enhancing Tumor as Biomarkers for Isocitrate Dehydrogenase-Mutant Glioblastoma: A Multicenter Study.

PURPOSE: This study aimed to investigate the most useful clinical and magnetic resonance imaging (MRI) parameters for differentiating isocitrate dehydrogenase (IDH)-mutant and -wildtype glioblastomas in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. METHODS: This multicenter study included 327 patients with IDH-mutant or IDH-wildtype glioblastoma in the 2016 World Health Organization classification who preoperatively underwent MRI. Isocitrate dehydrogenase mutation status was determined by immunohistochemistry, high-resolution melting analysis, and/or IDH1/2 sequencing. Three radiologists independently reviewed the tumor location, tumor contrast enhancement, noncontrast-enhancing tumor (nCET), and peritumoral edema. Two radiologists independently measured the maximum tumor size and mean and minimum apparent diffusion coefficients of the tumor. Univariate and multivariate logistic regression analyses with an odds ratio (OR) were performed. RESULTS: The tumors were IDH-wildtype glioblastoma in 306 cases and IDH-mutant glioblastoma in 21. Interobserver agreement for both qualitative and quantitative evaluations was moderate to excellent. The univariate analyses revealed a significant difference in age, seizure, tumor contrast enhancement, and nCET ( P < 0.05). The multivariate analysis revealed significant difference in age for all 3 readers (reader 1, odds ratio [OR] = 0.960, P = 0.012; reader 2, OR = 0.966, P = 0.048; reader 3, OR = 0.964, P = 0.026) and nCET for 2 readers (reader 1, OR = 3.082, P = 0.080; reader 2, OR = 4.500, P = 0.003; reader 3, OR = 3.078, P = 0.022). CONCLUSIONS: Age and nCET are the most useful parameters among the clinical and MRI parameters for differentiating IDH-mutant and IDH-wildtype glioblastomas.

Lymphomas of Central Nervous System.

Central nervous system (CNS) lymphoma consists of primary central nervous system lymphoma (PCNSL) and secondary CNS involvement by systemic lymphoma. This chapter focuses on the former. PCNSL is a relative rare disease, accounting for approximately 2.4-4.9% of all primary CNS tumors. It is an extra-nodal variant of non-Hodgkin's lymphoma (NHL), confined to the brain, leptomeninges, spinal cord, and eyes, with no systemic involvement. Recently, elderly patients (≥ 60 years) are increasing. Histologically, B cell blasts, which originate from late germinal center exit B cell, are growing and homing in CNS. Immunohistochemically, these cells are positive for PAX5, CD19, CD20, CD22, and CD79a. PCNSL shows relatively characteristic appearances on CT, MR imaging, and PET. Treatment first line of PCNSL is HD-MTX-based chemotherapy with or without rituximab and irradiation. Severe side-effect of this treatment is delayed onset neurotoxicity, which cause of cognitive impairment. Therefore, combined chemotherapy alone or chemotherapy with reduced-dose irradiation is more recommended for elderly patients. There is no established standard care for relapse of the PCNSLs. Temsirolimus, lenalidomide, temozolomide, and Bruton's tyrosine kinase (BTK) inhibitor ibrutinib are candidates for refractory patients. The prognosis of PCNSL has significantly improved over the last decades (median OS: 26 months, 5-year survival: 31%). Younger than 60 age and WHO performance status less than < or = 1 are associated with a significantly better overall survival.

Novel Strategy Involving High-Dose Chemotherapy with Stem Cell Rescue Followed by Intrathecal Topotecan Maintenance Therapy without Whole-Brain Irradiation for Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive central nervous system tumor that typically affects children under three years old and has poor survival with a high risk for neurologic deficits. The primary purpose of this study was to successfully treat the disease and delay or avoid whole-brain radiotherapy for children with AT/RT. A retrospective analysis was performed for six children diagnosed with AT/RT and treated with multimodal treatment at a single institute between 2014 and 2020. Furthermore, germline SMARCB1 aberrations and MGMT methylation status of the tumors were analyzed. One patient who did not receive a modified IRS-III regimen replaced with ifosphamide, carboplatin, and etoposide (ICE) in induction chemotherapy was excluded from this analysis. Five patients who received ICE therapy were under three years old. After a surgical approach, they received intensive chemotherapy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation (HDCT/autoPBSCT) followed by intrathecal topotecan maintenance therapy. Three patients underwent single HDCT/autoPBSCT, and the other two received sequential treatment. Two patients with germline SMARCB1 aberrations and metastases died of progressive AT/RT or therapy-related malignancy, while 3 with localized tumors without germline SMARCB1 aberrations remained alive. One survivor received local radiotherapy only, while the other two did not undergo radiotherapy. All three surviving patients were able to avoid whole-brain radiotherapy. Our results suggest that AT/RT patients with localized tumors without germline SMARCB1 aberrations can be rescued with multimodal therapy, including induction therapy containing ICE followed by HDCT/autoPBSCT and intrathecal topotecan maintenance therapy without radiotherapy. Further large-scale studies are necessary to confirm this hypothesis.

Hybrid deep-learning-based denoising method for compressed sensing in pituitary MRI: comparison with the conventional wavelet-based denoising method.

OBJECTIVES: This study aimed to evaluate the efficacy of a combined wavelet and deep-learning reconstruction (DLR) method for under-sampled pituitary MRI. METHODS: This retrospective study included 28 consecutive patients who underwent under-sampled pituitary T2-weighted images (T2WI). Images were reconstructed using either the conventional wavelet denoising method (wavelet method) or the wavelet and DLR methods combined (hybrid DLR method) at five denoising levels. The signal-to-noise ratio (SNR) of the CSF, hypothalamic, and pituitary images and the contrast between structures were compared between the two image types. Noise quality, contrast, sharpness, artifacts, and overall image quality were evaluated by two board-certified radiologists. The quantitative and the qualitative analyses were performed with robust two-way repeated analyses of variance. RESULTS: Using the hybrid DLR method, the SNR of the CSF progressively increased as denoising levels increased. By contrast, with the wavelet method, the SNR of the CSF, hypothalamus, and pituitary did not increase at higher denoising levels. There was a significant main effect of denoising methods (p < 0.001) and denoising levels (p < 0.001), and an interaction between denoising methods and denoising levels (p < 0.001). For all five qualitative scores, there was a significant main effect of denoising methods (p < 0.001) and an interaction between denoising methods and denoising levels (p < 0.001). CONCLUSIONS: The hybrid DLR method can provide higher image quality for T2WI of the pituitary with compressed sensing (CS) than the wavelet method alone, especially at higher denoising levels. KEY POINTS: • The signal-to-noise ratios of cerebrospinal fluid progressively increased with the hybrid DLR method, with an increase in the denoising level for cerebrospinal fluid in pituitary T2WI with CS. • The signal-to-noise ratios of cerebrospinal fluid using the conventional wavelet method did not increase at higher denoising levels. • All qualitative scores of hybrid deep-learning reconstructions at all denoising levels were higher than those for the wavelet denoising method.

Virtual Noncontrast Images Derived From Contrast-Enhanced Dual-Layer Spectral Abdominal Computed Tomography: A Pilot Study Between Pediatric and Adult Scans.

OBJECTIVE: We aimed to compare the accuracy of virtual noncontrast (VNC) images obtained from contrast-enhanced dual-layer spectral computed tomography (DLSCT) scans of the abdomen between pediatric and adult patients. METHODS: We retrospectively studied 10 pediatric and 40 adult patients who underwent unenhanced and contrast-enhanced DLSCT for nontraumatic acute abdomen or a follow-up of tumor or aneurysm. On true noncontrast (TNC) and VNC images, we placed a region-of-interest on 7 abdominal structures. The mean attenuation difference between VNC and TNC images was compared between these structures and between pediatric and adult scans. Data were analyzed by using the Wilcoxon signed-rank test, 1-way analysis of variance, Scheffe's test and independent t test. A P value less than 0.05 was considered statistically significant. RESULTS: In mean attenuation difference between VNC and TNC images, there was a significant interstructure difference in adult scans (P < 0.05), but not in pediatric scans. Mean attenuation difference between VNC and TNC images of the kidney was significantly higher on adult than pediatric scans (P = 0.0046). CONCLUSIONS: The VNC images obtained from contrast-enhanced DLSCT data may be more accurate on pediatric than adult scans. Patient age can be a factor influencing the accuracy of the VNC images.

Spectral imaging with dual-layer spectral detector computed tomography for the detection of perfusion defects in acute coronary syndrome.

To evaluate the feasibility of spectral imaging with dual-layer spectral detector computed tomography (CT) for the diagnosis of acute coronary syndrome. We identified 30 consecutive patients who underwent cardiac CT using dual-layer spectral detector CT and were diagnosed with acute ischemic syndrome by an invasive coronary angiography. We reconstructed 120 kVp images and generated virtual monochromatic images (VMIs; 40-200 keV in 10 keV increments), iodine concentration maps, and effective atomic number (Z) maps. We calculated the contrast and contrast-to-noise ratio (CNR) between myocardial normal and hypo-perfusion and chose the VMIs with the best CNR for quantitative analysis. We compared the image noise, contrast, and CNR of 120 kVp images and the best VMIs, CT value, iodine concentration, and effective Z between myocardial normal and hypo-perfusion with the paired t test. As the X-ray energy decreased, venous attenuation, contrast, and CNR gradually increased. The 40 keV image yielded the best CNR. The contrast and CNR between myocardial normal and hypo-perfusion were significantly higher in 40 keV images than those in 120 kVp images. The iodine concentration and the effective Z were significantly higher in normal myocardium than those in hypo-perfused myocardium. Spectral imaging with dual-layer spectral detector CT is a feasible technique to detect the hypo-perfused area of acute ischemic syndrome.

Detection of acute rib fractures on CT images with convolutional neural networks: effect of location and type of fracture and reader's experience.

PURPOSE: The evaluation of all ribs on thin-slice CT images is time consuming and it can be difficult to accurately assess the location and type of rib fracture in an emergency. The aim of our study was to develop and validate a convolutional neural network (CNN) algorithm for the detection of acute rib fractures on thoracic CT images and to investigate the effect of the CNN algorithm on radiologists' performance. METHODS: The dataset for development of a CNN consisted of 539 thoracic CT scans with 4906 acute rib fractures. A three-dimensional faster region-based CNN was trained and evaluated by using tenfold cross-validation. For an observer performance study to investigate the effect of CNN outputs on radiologists' performance, 30 thoracic CT scans (28 scans with 90 acute rib fractures and 2 without rib fractures) which were not included in the development dataset were used. Observer performance study involved eight radiologists who evaluated CT images first without and second with CNN outputs. The diagnostic performance was assessed by using figure of merit (FOM) values obtained from the jackknife free-response receiver operating characteristic (JAFROC) analysis. RESULTS: When radiologists used the CNN output for detection of rib fractures, the mean FOM value significantly increased for all readers (0.759 to 0.819, P = 0.0004) and for displaced (0.925 to 0.995, P = 0.0028) and non-displaced fractures (0.678 to 0.732, P = 0.0116). At all rib levels except for the 1st and 12th ribs, the radiologists' true-positive fraction of the detection became significantly increased by using the CNN outputs. CONCLUSION: The CNN specialized for the detection of acute rib fractures on CT images can improve the radiologists' diagnostic performance regardless of the type of fractures and reader's experience. Further studies are needed to clarify the usefulness of the CNN for the detection of acute rib fractures on CT images in actual clinical practice.

Usefulness of Virtual Monochromatic Images and Iodine Maps Derived from Dual-Energy Computed Tomography for Diagnosing Deep Neck Abscesses.

OBJECTIVE: We aimed to determine whether dual-energy computed tomography (CT) is useful for evaluating deep neck abscesses. METHODS: This study included 22 consecutive patients who were clinically suspected of having a deep neck abscess and underwent dual-energy CT. Conventional 120-kVp images, 70- and 40-keV virtual monochromatic images (VMIs), and iodine maps were inspected to calculate the contrast ratio of the abscess rim (AR) to the abscess center (AC) or to the adjacent muscle (M). The diagnostic certainty of abscesses was assessed on these images. RESULTS: Twenty (91%) of 22 patients had a definitive diagnosis. The contrast ratio for AR/AC and AR/M was significantly higher on 40-keV VMIs and iodine maps than on 120-kVp images and 70-keV VMIs (P < 0.05). On both 40-keV VMIs and iodine maps, the diagnostic certainty of abscess improved in 3 (15%) cases compared with 120-kVp images and 70-keV VMIs. CONCLUSIONS: Dual-energy CT-based 40-keV VMIs and iodine maps are useful for evaluating deep neck abscesses and may improve diagnostic certainty.

Conditional unnecessity of head CT for whole-body CT of traffic accident victims: a pilot study.

PURPOSE: To investigate whether head CT should be included in whole-body CT in road traffic accident victims. METHODS: A review of electronic medical records identified 124 patients (81 males, 43 females; age 4 to 92 years, mean 47.7 years) involved in a road traffic accident in a 12-month period. All had undergone whole-body CT and physical and neurologic examinations. We recorded their age, sex, Glasgow Coma Scale (GCS), systolic blood pressure (SBP), the type of traffic accident, and the presence/absence of visible trauma above the clavicles (VTCs) and of acute traumatic brain injury (TBI) on CT. Statistical analyses were performed to evaluate predictors of acute TBI. RESULTS: Of 124 patients, 34 (27%) manifested acute TBI on CT. Univariate analysis identified their age, GCS, SBP, VTCs, and the accident type as statistically significant factors for acute TBI (p < 0.05). Multivariate analysis demonstrated VTCs, GCS score < 15, and SBP ≤ 90 mmHg were significant independent predictors of acute TBI (p = 0.001, p = 0.001, and p = 0.004, respectively); the odds ratio was 16.07 for VTCs, 14.85 for GCS score < 15, and 13.78 for SBP ≤ 90 mmHg. No patients without both decrease in GCS score and VTCs manifested acute TBI. CONCLUSION: Our pilot study showed that visible trauma above the clavicles and decrease in GCS score were highly associated with the presence of acute TBI in road traffic accident victims. In whole-body CT, a head CT may not be indicated in patients without these factors.

Short-term experience with aspiration embolectomy using a ACE68 reperfusion catheter to treat embolic superior mesenteric artery occlusion.

We report the short-term results with aspiration embolectomy using an ACE68 reperfusion catheter to treat patients with acute embolic superior mesenteric artery (SMA) occlusion. Our study included 4 consecutive male patients ranging in age from 72 to 86 years (mean age 79 years). In all patients, the main trunk of the SMA was occluded. The technical success rate was 100% for all procedures. There were no major procedure-related complications. One patient underwent laparotomy with intestinal resection after successful recanalization. No patient reported clinical symptoms of abdominal ischemia at follow-up. Our short-term experience shows that percutaneous aspiration embolectomy using an ACE68 reperfusion catheter is an effective treatment for acute mesenteric ischemia.

Differentiation between glioblastoma and solitary brain metastasis using neurite orientation dispersion and density imaging.

BACKGROUND AND PURPOSE: Neurite orientation dispersion and density imaging (NODDI) is a new technique that applies a three-diffusion-compartment biophysical model. We assessed the usefulness of NODDI for the differentiation of glioblastoma from solitary brain metastasis. METHODS: NODDI data were prospectively obtained on a 3T magnetic resonance imaging (MRI) scanner from patients with previously untreated, histopathologically confirmed glioblastoma (n = 9) or solitary brain metastasis (n = 6). Using the NODDI Matlab Toolbox, we generated maps of the intra-cellular, extra-cellular, and isotropic volume (VIC, VEC, VISO) fraction. Apparent diffusion coefficient - and fraction anisotropy maps were created from the diffusion data. On each map we manually drew a region of interest around the peritumoral signal-change (PSC) - and the enhancing solid area of the lesion. Differences between glioblastoma and metastatic lesions were assessed and the area under the receiver operating characteristic curve (AUC) was determined. RESULTS: On VEC maps the mean value of the PSC area was significantly higher for glioblastoma than metastasis (P < 0.05); on VISO maps it tended to be higher for metastasis than glioblastoma. There was no significant difference on the other maps. Among the 5 parameters, the VEC fraction in the PSC area showed the highest diagnostic performance. The VEC threshold value of ≥ 0.48 yielded 100% sensitivity, 83.3% specificity, and an AUC of 0.87 for differentiating between the two tumor types. CONCLUSIONS: NODDI compartment maps of the PSC area may help to differentiate between glioblastoma and solitary brain metastasis.

Circumventricular organs of human brain visualized on post-contrast 3D fluid-attenuated inversion recovery imaging.

PURPOSE: Although contrast-enhanced three-dimensional T2 fluid-attenuated inversion recovery (3D T2-FLAIR) images are useful for assessing various neuronal diseases, physiological enhancement of the circumventricular organs on the images have not been investigated. We aimed to assess the physiological appearance of the circumventricular organs on contrast-enhanced 3D T2-FLAIR images. METHODS: We studied 3-T MR images of the brain of 30 individuals with no apparent brain abnormalities. In ten areas of the brain, the degree of contrast enhancement on 3D T2-FLAIR and magnetization-prepared rapid gradient-echo (MPRAGE) images was evaluated using a 4-point grading system. The pre- and post-contrast mean contrast ratios (CRs) of the anterior pituitary gland, median eminence, and pineal gland were compared. RESULTS: On post-contrast 3D T2-FLAIR images, marked enhancement was most frequently scored in the median eminence, followed by the choroid plexus, posterior pituitary gland, and pineal gland. In 10 of the 30 cases, the vascular organ of the lamina terminalis and the area postrema were enhanced but the subcommissural organ was not. The difference in the mean pre- and post-contrast CRs of the median eminence and pineal gland was statistically significant, while that of the anterior pituitary gland was not. CONCLUSION: On contrast-enhanced 3D T2-FLAIR images, the circumventricular organs show variable enhancement. Our findings help to recognize physiological and abnormal enhancement of brain structures on contrast-enhanced 3D T2-FLAIR images.

Evaluation of Intracranial Arteriovenous Malformations With Four-Dimensional Arterial-Spin Labeling-Based 3-T Magnetic Resonance Angiography.

OBJECTIVE: We aimed to assess the usefulness of 3-T 4-dimensional (4D) arterial spin-labeling (ASL)-based magnetic resonance angiography (MRA) with color-coded time-of-arrival (TOA) maps for the evaluation of cerebral arteriovenous malformations (AVMs). METHODS: Our study included 6 patients with cerebral AVMs. They underwent 4D-ASL MRA at 3T and digital subtraction angiography. A pseudocontinuous arterial spin labeling protocol with look-locker sampling was used for spin labeling. Two independent readers reviewed the 4D-ASL MRA images with color-coded TOA maps for the nidus size, arterial feeders, and venous drainage. Two other readers consensually reviewed the digital subtraction angiography images. RESULTS: The cerebral AVMs were demonstrated on all 4D-ASL MRA images. In 5 high-flow AVMs, the color-coded TOA maps were especially useful for identifying the feeder/drainer. Intermodality agreement was excellent for the nidus size (κ = 1.0), very good for arterial feeders (κ = 0.88), and good for venous drainage (κ = 0.80). CONCLUSIONS: The 4D-ASL 3-T MRA with color-coded TOA maps is useful for assessing the gross angiographic characteristics of intracranial AVMs.

Collateral circulation via the circle of Willis in patients with carotid artery steno-occlusive disease: evaluation on 3-T 4D MRA using arterial spin labelling.

AIM: To evaluate whether 3-T four-dimensional (4D) arterial spin-labelling (ASL) -based magnetic resonance angiography (MRA) is useful for assessing the collateral circulation via the circle of Willis in patients with carotid artery steno-occlusive disease. MATERIALS AND METHODS: Institutional review board approval and prior written informed consent from all patients were obtained. The inclusion criteria were fulfilled by 13 patients with carotid artery steno-occlusive disease. All underwent 4D-ASL MRA at 3 T and digital subtraction angiography (DSA). The flow-sensitive alternating inversion recovery (FAIR) preparation scheme with look-locker sampling was used for spin labeling. At 300-ms intervals seven dynamic scans were obtained with a spatial resolution of 0.5×0.5×0.6 mm(3). The collateral flow via the circle of Willis was read on 4D-ASL MRA and DSA images by two sets of two independent readers each. κ statistics were used to assess interobserver and intermodality agreement. RESULTS: On DSA, collateral flow via the anterior communicating artery (AcomA) was observed in six patients, via the posterior communicating artery (PcomA) in four patients, and via both the AcomA and PcomA in three patients. With respect to the qualitative evaluation of 4D-ASL MRA images, interobserver agreement was excellent for all items (κ=1). 4D-ASL MRA and DSA consensus readings agreed on the type of collateral flow pattern in 10 of the 13 patients (77%). Intermodality agreement was good (κ=0.606; 95% confidence interval (CI): 0.215-0.997). CONCLUSION: 3 T 4D-ASL MRA may be a useful tool for the evaluation of the collateral circulation in patients with carotid artery steno-occlusive disease.

Intracranial dural arteriovenous fistulas: evaluation with 3-T four-dimensional MR angiography using arterial spin labeling.

PURPOSE: To evaluate whether 3-T four-dimensional (4D) arterial spin-labeling (ASL)-based magnetic resonance (MR) angiography is useful for the evaluation of shunt lesions in patients with intracranial dural arteriovenous fistulas (AVFs). MATERIALS AND METHODS: Institutional review board approval and prior written informed consent from all patients were obtained. Nine patients with intracranial dural AVF (seven men, two women; age range, 52-77 years; mean age, 63 years) underwent 4D ASL MR angiography at 3 T and digital subtraction angiography (DSA). Spin tagging was with flow-sensitive alternating inversion recovery with Look-Locker sampling. At 300-millisecond intervals, seven dynamic images with a spatial resolution of 0.5 × 0.5 × 0.6 mm(3) were obtained. The 4D ASL MR angiographic and DSA images were read by two sets of two independent readers each. Interobserver and intermodality agreement was assessed with the κ statistic. RESULTS: On all 4D ASL MR angiographic images, the major intracranial arteries were demonstrated at a temporal resolution of 300 milliseconds. Interobserver agreement was excellent for the fistula site (κ = 1.00; 95% confidence interval [CI]: 1.00, 1.00), moderate for the main arterial feeders (κ = 0.53; 95% CI: 0.08, 0.98), and good for venous drainage (κ = 0.77; 95% CI: 0.35, 1.00). Intermodality agreement was excellent for the fistula site and venous drainage (κ = 1.00; 95% CI: 1.00, 1.00) and good for the main arterial feeders (κ = 0.80; 95% CI: 0.58, 1.00). CONCLUSION: The good-to-excellent agreement between 3-T 4D ASL MR angiographic and DSA findings suggests that 3-T 4D ASL MR angiography is a useful tool for the evaluation of intracranial dural AVFs.

A case of multifocal sclerosis angiomatoid nodular transformations of the spleen occurring after partial splenic infarction with transcatheter arterial embolization for splenic artery aneurysm.

A 48-year-old woman underwent transcatheter arterial embolization (TAE) for a splenic artery aneurysm, which resulted in a partial splenic infarction in the middle lobe. Five years after TAE, a 20-mm diameter mass in the noninfarcted area of the spleen was detected on imaging, which grew to 25 mm in diameter after 6 months. MRI after gadolinium administration showed a 35 × 34 mm mass within the superior pole and 15 × 12 mm mass within the inferior pole. The patient underwent laparoscopic splenectomy and had an uneventful postoperative recovery. No evidence of recurrence was observed during the 2-year follow-up period after surgery. The mass was pathologically confirmed to be sclerosing angiomatoid nodular transformation (SANT) of the spleen. While some studies hypothesize that SANT is a response to vascular injury or trauma, to the best of our knowledge, there have been no previous reports of SANT occurring after procedures directly affecting splenic blood flow. Additionally, multifocal SANTs are reported to be very rare, accounting for only 4.7% of all reported SANTs of the spleen. We highlight a rare course of SANT of the spleen and discuss the possible relationship between blood flow abnormalities and the appearance of SANT.

Elevated plasma levels of factor VIII enhance arterial thrombus formation on erosive smooth muscle cell-rich neointima but not normal intima in rabbits.

BACKGROUND: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques. AIMS: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits. METHODS AND RESULTS: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5'-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group. CONCLUSIONS: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis.

Expression of fibroblast activation protein-α in human deep vein thrombosis.

BACKGROUND: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT. METHODS: We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts. RESULTS: All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin. CONCLUSIONS: The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.

Added value of high-b-value (b = 3000 s/mm2) diffusion-weighted imaging at 3 T in relation to fluid-attenuated inversion recovery images for the evaluation of cortical lesions in inflammatory brain diseases.

OBJECTIVE: The purpose of this study was to determine how the gray-to-white matter contrast in healthy subjects changes on high-b-value diffusion-weighted imaging (DWI) acquired at 3 T and evaluate whether high-b-value DWI at 3 T is useful for the detection of cortical lesions in inflammatory brain diseases. METHODS: Ten healthy volunteers underwent DWI at b = 1000, 2000, 3000, 4000, and 5000 s/mm(2) on a 3-T MRI unit. On DW images, 1 radiologist performed region-of-interest measurements of the signal intensity of 8 gray matter structures. The gray-to-white matter contrast ratio (GWCR) was calculated. Ten patients with inflammatory cortical lesions were also included. All patients underwent conventional MRI and DWI at b = 1000 and 3000 s/mm(2). Using a 4-point grading system, 2 radiologists independently assessed the presence of additional information on DW images compared with fluid-attenuated inversion recovery images. Interobserver agreement was assessed by κ statistics. RESULTS: In the healthy subjects, the b value increased as the GWCR decreased in all evaluated gray matter structures. On DW images acquired at b = 3000 s/mm(2), mean GWCR was less than 1.0 in 7 of 8 structures. For both reviewers, DWI at b = 3000 s/mm(2) yielded significantly more additional information than did DWI at b = 1000 s/mm(2) (P < 0.05). Interobserver agreement for DWI at b = 1000 s/mm(2) and b = 3000 s/mm(2) was fair (κ = 0.35) and excellent (κ = 1.0), respectively. CONCLUSIONS: At 3-T DWI, the gray-to-white matter contrast in most gray matter structures reverses at b = 3000 s/mm. In the evaluation of cortical lesions in patients with inflammatory brain diseases, 3-T DWI at b = 3000 s/mm was more useful than b = 1000 s/mm(2).