Different hemodynamics of basal ganglia between moyamoya and non-moyamoya diseases using intravoxel incoherent motion imaging and single-photon emission computed tomography.

BACKGROUND: Moyamoya disease (MMD) and non-MMD have different pathogenesis, clinical presentation, and treatment policy. PURPOSE: To identify differences in hemodynamics between MMD and non-MMD using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). MATERIAL AND METHODS: Patients who had undergone 99mTc-ECD or 123I-IMP SPECT, and IVIM imaging were retrospectively studied. IVIM imaging was acquired using six different b-values. Cerebral blood flow ratio (CBFR) in the basal ganglia was calculated using a standardized volume-of-interest template. The cerebellum was used as a reference region. IVIM perfusion fraction (f) was obtained using a two-step fitting algorithm. Elliptical regions of interest were placed in bilateral basal ganglia on the IVIM f map. Patients were classified into MMD and non-MMD groups. The correlation between CBFR and mean IVIM f (fmean) in the basal ganglia was evaluated using Spearman's rank correlation coefficient. RESULTS: In total, 20 patients with MMD and 28 non-MMD patients were analyzed. No significant differences in fmean were observed among MMD, affected hemisphere with non-MMD (non-MMDaff), and unaffected hemispheres with non-MMD (non-MMDunaff). A negative correlation was seen between fmean and CBFR in the MMD group (r = -0.40, P = 0.0108), but not in the non-MMD group (non-MMDaff, r = 0.07, P = 0.69; non-MMDunaff, r = -0.22, P = 0.29). No significant differences were found among MMD and non-MMD patients, irrespective of SPECT tracers. CONCLUSION: The combination of IVIM MRI and SPECT appears to allow non-invasive identification of differences in hemodynamics between MMD and non-MMD.

Early-onset hepatic veno-occlusive disease after liver transplantation: an institutional experience and analysis of a literature-based cohort.

PURPOSE: Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort. METHODS: We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a "pooled" cohort of cases identified in our institute and reported in the literature. RESULTS: HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively. CONCLUSION: Early-onset HVOD developing within 14 days after LT has a poor prognosis.

Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features.

AIM: Emerging evidence suggests a promising role for tumor stromal factors in characterizing patients with various types of malignancies, including hepatocellular carcinoma (HCC). We quantified the amount of collagen and elastin fibers in HCC samples with the aim of clarifying the clinico-patho-radiological significance of fiber deposition in HCC. METHODS: We computed the amount of collagen and elastin fibers using digital image analysis of whole-slide images of Elastica van Gieson-stained tissues from 156 surgically resected HCCs. Furthermore, we assessed the correlations between the fiber content of HCC samples and clinical, pathological, and radiological features, including immunohistochemistry-based molecular subtypes and immunosubtypes. RESULTS: The intratumoral area ratio of collagen in HCC tissues (median 3.4%, range 0.1-22.2%) was more than threefold that of elastin (median 0.9%, range 0.1-9.0%); there was a strong positive correlation between the amounts of collagen and elastin. Higher levels of combined collagen and elastin were significantly associated with the confluent multinodular macroscopic tumor type, the absence of a fibrous capsule, intratumoral steatosis, scirrhous tumor stroma, dense inflammatory-cell infiltrates, and the biliary/stem cell markers-positive HCC subtype. The associations of higher collagen levels with radiological findings, including heterogeneous enhancement and persistent enhancement on dynamic computed tomography, were significant. In contrast, the associations of radiological findings with elastin fibers were not significant. Intratumoral fibrous stroma in HCC comprised septum-like and perisinusoidal fibrosis; these two forms represented distinct distribution patterns of fibers and fibroblasts. CONCLUSION: Quantitative analysis suggested that stromal fiber-rich HCCs likely represent a distinct clinico-patho-radiological entity.

Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification.

Immune cells constitute an important element of tumor tissue. Accumulating evidence indicates their clinicopathological significance in predicting prognosis and therapeutic efficacy. Nonetheless, the combinations of immune cells forming the immune microenvironment and their association with histological findings remain largely unknown. Moreover, it is unclear which immune cells or immune microenvironments are the most prognostically significant. Here, we comprehensively analyzed the immune microenvironment and its intratumor heterogeneity in 919 regions of 158 hepatocellular carcinomas (HCCs), and the results were compared with the corresponding histological and prognostic data. Consequently, we classified the immune microenvironment of HCC into three distinct immunosubtypes: Immune-high, Immune-mid, and Immune-low. The Immune-high subtype was characterized by increased B-/plasma-cell and T cell infiltration, and the Immune-high subtype and B-cell infiltration were identified as independent positive prognostic factors. Varying degrees of intratumor heterogeneity of the immune microenvironment were observed, some of which reflected the multistep nature of HCC carcinogenesis. However, the predominant pattern of immunosubtype and immune cell infiltration of each tumor was prognostically important. Of note, the Immune-high subtype was associated with poorly differentiated HCC, cytokeratin 19 (CK19)+ , and/or Sal-like protein 4 (SALL4)+ high-grade HCC, and Hoshida's S1/Boyault's G2 subclasses. Furthermore, patients with high-grade HCC of the predominant Immune-high subtype had significantly better prognosis. These results provide a rationale for evaluating the immune microenvironment in addition to the usual histological/molecular classification of HCC. CONCLUSION: The immune microenvironment of HCC can be classified into three immunosubtypes (Immune-high, Immune-mid, and Immune-low) with additional prognostic impact on histological and molecular classification of HCC. (Hepatology 2018).

Additive value of "otosclerosis-weighted" images for the CT diagnosis of fenestral otosclerosis.

Background Otosclerotic foci are usually seen as minute low-density lesions and this may be attributed to relatively low sensitivity on visual assessment using computed tomography (CT). Otosclerotic foci can be detected by using the accurate region of interest (ROI) setting, while small ROI settings by less-experienced radiologists may result in false negative findings. Purpose To evaluate the diagnostic ability of our proposed method ("otosclerosis-weighted" imaging [OWI]), which is based on reversing the density, compared with conventional CT (CCT) imaging alone. Material and Methods Temporal bone CTs of consecutive patients with otosclerosis were analyzed. Gender- and age-matched control participants were also included. All CT images were obtained using a 64-detector row scanner. OWI was obtained by extracting the temporal bone region using the threshold technique and reversing the density (black to white). Four independent radiologists took part in two reading sessions. In the first session, the observers read only CCT imaging. In the second session, they read OWI along with the CCT imaging. Sensitivity was assessed for the four readers. Results Thirty temporal bones of 25 patients with otosclerosis (3 men, 22 women; mean age, 53.9 ± 9.0 years) and 30 temporal bones of 30 control participants (4 men, 26 women; mean age, 44.0 ± 16.2 years) were included. For all observers, reading with a combination of the two methods was associated with a higher sensitivity (63.3-80.0%) than with conventional CT images alone (30.0-60.0%; P < 0.05, each). Conclusion Application of our proposed method based on threshold value may help detect foci of fenestral otosclerosis.

Multiparametric assessment of microvascular invasion in hepatocellular carcinoma using gadoxetic acid-enhanced MRI.

PURPOSE: To elucidate how precisely microvascular invasion (MVI) in hepatocellular carcinoma (HCC) can be predicted using multiparametric assessment of gadoxetic acid-enhanced MRI. METHODS: In this retrospective single-center study, patients who underwent liver resection or transplantation of HCC were evaluated. Data obtained in patients who underwent liver resection were used as the training set. Nine kinds of MR findings for predicting MVI were compared between HCCs with and without MVI by univariate analysis, followed by multiple logistic regression analysis. Using significant findings, a predictive formula for diagnosing MVI was obtained. The diagnostic performance of the formula was investigated in patients who underwent liver resection (validation set 1) and in patients who underwent liver transplantation (validation set 2) using a receiver operating characteristic curve analysis. The area under the curves (AUCs) of these three groups were compared. RESULTS: A total of 345 patients with 356 HCCs were selected for analysis. Tumor diameter (D) (P = 0.021), tumor washout (TW) (P < 0.01), and peritumoral hypointensity in the hepatobiliary phase (PHH) (P < 0.01) were significantly associated with MVI after multivariate analysis. The AUCs for predicting MVI of the predictive formula were as follows: training set, 0.88 (95% confidence interval (CI) 0.82,0.93); validation set 1, 0.81 (95% CI 0.73,0.87); validation set 2, 0.67 (95% CI 0.51,0.80). The AUCs were not significantly different among three groups (training set vs validation set 1; P = 0.15, training set vs validation set 2; P = 0.09, validation set 1 vs validation set 2; P = 0.29, respectively). CONCLUSION: Our multiparametric assessment of gadoxetic acid-enhanced MRI performed quite precisely and with good reproducibility for predicting MVI.

Current status and challenges of percutaneous vertebroplasty (PVP).

A narrative review regarding percutaneous vertebroplasty (PVP) for osteoporotic vertebral fracture (OVF) is provided herein, addressing the epidemic of OVF in Japan, the latest response to the criticism of PVP for OVFs, the indications and potential risks of PVP for OVFs, and a future perspective for PVP. Each year in Japan, approximately 32,000 patients aged 55 years or older suffer from chronic low back pain for several months to several years due to a compression fracture. PVP is one of the surgical treatments for an OVF, and it is less invasive compared to the traditional open surgery. PVP is suitable for OVF patients who have difficulty walking as assessed by the modified Yokoyama's activities of daily living (ADL) scoring system, and for patients with Kummell's disease diagnosed by CT and MRI examinations. Serious adverse events related to PVP occur in 1.1-3.3% of the cases, but direct deaths from PVP are extremely rare at less than 1%. Recent studies demonstrated that OVF patients treated with PVP are less likely to die after the treatment than non-surgically treated patients, which conflicts with the Cochran reviews' conclusion not supporting PVP for OVFs. Novel robotic systems and procedure-support devices are being developed, providing a next step toward fully automated PVP procedures.

Extracellular volume fraction determined by equilibrium contrast-enhanced computed tomography: correlation with histopathological findings in gastric cancer.

PURPOSE: To assess the relationship between histopathological features of gastric cancer and the extracellular volume fraction (ECV) measured by preoperative equilibrium contrast-enhanced computed tomography (CECT). MATERIALS AND METHODS: The study group consisted of 66 patients with surgically resected gastric adenocarcinoma who underwent preoperative multiphasic CECT. Tumor ECVs were calculated using region-of-interest measurements within the gastric cancer and aorta of each case on unenhanced and equilibrium-phase images. The relationship between the mean ECV values and clinicopathological parameters was examined by univariate analysis. Parameters showing a significant difference in the former test were further tested by linear regression and receiver operating characteristic (ROC) curve analyses. RESULTS: In the univariate analysis, the values of venous invasion (p = 0.0487) and tumor infiltration (INF) pattern (p < 0.0001) were significantly correlated with the tumor ECV. INF was significantly correlated (ß = 0.57, p < 0.0001) in the linear regression analysis. The tumor ECV showed better diagnostic accuracy for predicting INF (INFa/b vs INFc), and the area under the ROC curve value was 0.89. CONCLUSION: Tumor ECV determined by equilibrium CECT is significantly correlated with the pathological INF of gastric cancer.

Analysis of "visible in retrospect" to monitor false-negative findings in radiological reports.

PURPOSE: False-negative findings in radiological reports can lead to serious adverse patient outcomes. We determined the frequency and tendency of false-negative findings in radiological reports by searching for words related to "visible in retrospect". METHODS: In the period of 34 months, we extracted radiological reports containing words related to "visible in retrospect". Of these reports, we extracted false-negative findings that were not described in past reports and were first detected retrospectively. Misinterpretations were excluded. The occurrences of the terms that we identified were analyzed by all examinations, modality, month, and anatomical and lesion classifications were analyzed. RESULTS: Of the 135,251 examinations, 941 reports (0.71%) with 962 findings were detected, with an average of 1.4 findings per business day. By modality, 713 of 81,899 (0.87%) CT examinations, 208 of 36,174 (0.57%) MR, 34 of 9,585 (0.35%) FDG-PET-CT, 2 of 2,258 (0.09%) digital radiography, and 5 of 5,335 (0.09%) other nuclear medicine examinations were found. By anatomical classification, there were 383 (40%) in chest, 353 (37%) in abdomen, 162 (17%) in head, 42 (4.4%) in face and neck, 9 (0.93%) in extremity, and 13 (1.4%) in others. By lesion classification, we identified 665 (69%) for localized lesion, 170 (18%) for vascular lesion, 83 (8.6%) for inflammatory lesion, 14 (1.5%) for traumatic lesion, 12 (1.2%) for organ dysfunction, 11 (1.1%) for degenerative lesion, and 7 (0.7%) for the others. Notable high-frequency specific site diseases by modality were 210 (22%) of localized lesions in lung on CT. CONCLUSION: Our results demonstrated that missed lung localized lesions on CT, which account for about a fifth of false-negative findings, were the most common false-negative finding.

Accuracy of vertebral puncture in percutaneous vertebroplasty.

PURPOSE: To clarify the accuracy of vertebral puncture of the vertebral tertile area needling (VETERAN) method puncturing the pedicle superimposed on one-third of the width between the lateral vertebral line to the contralateral medial lamina line compared with Cathelin-needle-assisted puncture (CAP) method puncturing using the Cathelin needle as a guide in percutaneous vertebroplasty. MATERIALS AND METHODS: 449 punctures by CAP method and 125 punctures by VETERAN method were enrolled. We compared the puncture accuracy of both methods. We estimated a vertebral estimated tilting ratio (VET-ratio) defined as ratio of the distance between the lateral vertebral line and the contralateral medial laminal line to the distance between the vertebral lateral line and the puncture point measured by computed tomography. We also estimated the procedural items and clinical outcomes. RESULTS: VETERAN method with 100% of punctures within safe zone (cortical breaches within 2 mm) had significantly higher accuracy than CAP method with 97.8% (p < 0.01) for the 2 mm incremental evaluation. No cases with a VET-ratio of 36% or less had cortical breaches. VETERAN method had shorter operative time per puncture (p < 0.01) and exposure time per puncture (p < 0.05). CONCLUSION: VETERAN method reduced the occurrence of the inaccurate puncture, operative times, and exposure times. A VET-ratio with 36% or less is associated with a safe puncture using VETERAN method.

Diagnostic potential of T1ρ and T2 relaxations in assessing the severity of liver fibrosis and necro-inflammation.

PURPOSE: To investigate the utility of T1ρ and T2 relaxations for assessing the severity of liver fibrosis (F stage) and necro-inflammation (A stage) in patients with chronic liver disease (CLD). MATERIALS AND METHODS: We calculated T1ρ and T2 relaxations of the liver parenchyma in 82 patients who underwent liver surgery. F and A stages of enrolled patients were assessed by referring to surgically resected specimens. The relationships between T1ρ or T2 relaxation and F or A stage were assessed using one-way analysis of variance followed by Tukey's multiple comparison test, Spearman's rank correlation test and a receiver operating characteristic analysis. RESULTS: The T1ρ and T2 values of the liver parenchyma were significantly increased as the F and A stages progressed. The T1ρ and T2 values showed significant differences between F0 and F4, between F1 and F4, and between F2 and F4. In addition, T1ρ values showed a significant difference between F0 and F3 as well. The highest diagnostic ability for fibrosis was obtained when differentiating ≥F3 from ≤F2 using T1ρ: the sensitivity was 82.8%, the specificity 79.2% and the area under the curve (AUC) 0.87. The sensitivity and AUC of T1ρ relaxation (46.9% and 0.67) were significantly higher than those of T2 relaxation (29.7% and 0.60) for differentiating ≥A1 from A0. CONCLUSION: T1ρ and T2 relaxations have potential as a biochemical marker for assessing the severity of liver fibrosis and necro-inflammation. T1ρ relaxation may be slightly superior to T2 relaxation in terms of diagnostic ability for liver fibrosis and necro-inflammation.

Noninvasive assessment of liver fibrosis by dual-layer spectral detector CT.

PURPOSE: To elucidate the diagnostic ability of liver fibrosis using (1) liver parenchymal iodine density on equilibrium computed tomographic imaging and (2) extracellular volume (ECV) measured by dual-layer spectral detector CT. METHODS: From April 2018 to June 2019, 68 patients [mean age, 62 years; 39 males, 29 females] underwent dynamic contrast-enhanced CT by a dual-layer spectral detector CT system before liver transplantation or liver resection. The iodine densities of liver parenchyma (I liver) and aorta (I aorta) were independently measured by two radiologists at the equilibrium phase. The iodine-density ratio (I-ratio) (I liver/ I aorta) and the CT-ECV were calculated. Spearman's rank correlation coefficient was used to analyze the relationship between the I-ratio or the CT-ECV and the fibrosis stage. A receiver operating characteristic (ROC) curve analysis was performed to determine the accuracy of the I-ratio and the CT-ECV for discriminating fibrosis stages. RESULTS: For both readers, the I-ratio and the CT-ECV increased significantly as the fibrosis stage advanced (I-ratio: rho = 0.380 and 0.443, p < 0.01; CT-ECV: rho = 0.423 and 0.469, p < 0.01). The CT-ECV showed better diagnostic accuracy for staging fibrosis, and the area under the ROC curve values for discriminating F4 stage were 0.884 and 0.925. The two readers' cutoff values of the CT-ECV for diagnosing fibrosis as F4 were 26.2 % and 29.3 %, with 95.0 % and 90.0 % sensitivity and 72.9 % and 85.4 % specificity, respectively. CONCLUSION: The liver parenchymal iodine density on the equilibrium phase and the CT-ECV can be useful for predicting a high stage of liver fibrosis.

Tumor microenvironment in giant cell tumor of bone: evaluation of PD-L1 expression and SIRPα infiltration after denosumab treatment.

Giant cell tumor of bone (GCTB) is an intermediate malignant bone tumor that is locally aggressive and rarely metastasizes. Denosumab, which is a receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor, can be used to treat GCTB. We focused on potential immunotherapy for GCTB and investigated the tumor microenvironment of GCTB. Programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) expression and signal-regulatory protein alpha (SIRPα), forkhead box P3 (FOXP3), and cluster of differentiation 8 (CD8) infiltration were assessed by immunohistochemical studies of 137 tumor tissues from 96 patients. Of the naive primary specimens, 28% exhibited PD-L1 expression and 39% exhibited IDO1 expression. There was significantly more SIRPα+, FOXP3+, and CD8+ cell infiltration in PD-L1- and IDO1-positive tumors than in PD-L1- and IDO1-negative tumors. The frequency of PD-L1 expression and SIRPα+ cell infiltration in recurrent lesions treated with denosumab was significantly higher than in primary lesions and recurrent lesions not treated with denosumab. PD-L1 expression and higher SIRPα+ cell infiltration were significantly correlated with shorter recurrence-free survival. PD-L1 and SIRPα immune checkpoint inhibitors may provide clinical benefit in GCTB patients with recurrent lesions after denosumab therapy.

Tumor Enhancement on Dynamic CT: A Predictive Factor for Recurrence After Nephrectomy in Localized T1 Clear Cell Renal Cell Carcinoma.

AIM: To investigate whether radiological parameters obtained on dynamic computed tomography (CT), especially those related to tumor enhancement, are predictive factors for recurrence after nephrectomy in localized stage T1 clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We retrospectively studied 88 patients with localized stage T1 ccRCC who underwent dynamic CT preoperatively. Seven patients had recurrent disease after surgery. Tumor attenuations were measured by placing a region of interest in the solid region. TApre and TAneph were defined as the tumor attenuation values of the pre-contrast and nephrographic phase, respectively. The correlations between disease-free survival and clinicopathological factors, including the radiological parameter TAneph - TApre (ΔTAneph), were analyzed by Cox proportional hazards model or Kaplan-Meier method with the log-rank test. RESULTS: Only ΔTAneph was significantly and positively correlated with disease-free survival (p<0.05). Tumor size also tended to be negatively correlated with disease-free survival (p<0.1). The 5- and 10-year disease-free survival rates of the group with high ΔTAneph (≥86 HU) were 97.4% and 97.4%, while those of the group with low ΔTAneph (<86 HU) were 89.6% and 71.6%, respectively. CONCLUSION: Tumor enhancement in the nephrographic phase of CT was a predictive factor for recurrence after nephrectomy in patients with localized stage T1 ccRCC.

Primary phosphaturic mesenchymal tumour of the lumbar spine: utility of 68Ga-DOTATOC PET/CT findings.

Primary phosphaturic mesenchymal tumours (PMTs) frequently occur in the soft tissue or bone, but rarely in the spine. The majority of patients experience long-term ostalgia and recurrent fractures. Detection of PMT can be challenging, but the clinical symptoms dramatically improve after removal of the tumour.Wepresent a case of primary PMT in the lumbar spine. CT scan showed a low-density tumour with a well-defined sclerotic margin in the L5 vertebra. MRI revealed a hypointense tumour on T2 weighted imaging and heterogeneous enhancement. 68Ga-labelled 1,4,7,10-tetraazacyclododecane-N,N',N″, N‴-tetraacetic acid-D-Phe1-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography/CT scan demonstrated intense focal uptake within the tumour. Histologically, proliferation of oval to short spindle-shaped cells with fibrocollagenous stroma, abundant various-sized vessels, microcysts and thickened anastomosed bone trabeculae were seen. Mitotic figures were rarely seen. Immunohistochemically, the tumour cells were focally positive for fibroblast growth factor 23. The imaging findings in the current case are in accordance with the histological features. Among them, 68Ga-DOTATOC positron emission tomography/CT scan for somatostatin receptor imaging provides valuable information for determining PMT localization and characterization.