MRI detection of mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) on T1WI-CHESS.

Mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE) is a recently proposed epileptogenic entity that is difficult to detect on MRI. We present a case of MOGHE that was successfully detected on T1WI-chemical shift-selective saturation (CHESS) MRI. The clinical presentation, MRI including T1WI-CHESS, functional images, and pathology findings of a 14-year-old Japanese girl diagnosed with MOGHE are described. T1WI-CHESS revealed an abnormal high signal along the affected lesion, whereas the findings shown by the other MR sequences were less obvious; interictal fluorodeoxyglucose-positron emission tomography indicated slightly decreased accumulation in the lesion, and subtraction ictal single photon emission computed tomography co-registered to MRI showed an increased blood flow. Together these observations suggest that T1WI-CHESS may be a useful MR sequence for detecting the lesions in patients with MOGHE.

Dural Arteriovenous Fistula Mimicking Acute Encephalitis.

We herein report a case of acute neurological symptoms and a fever initially suspected of being encephalitis but later revealed to be dural arteriovenous fistula (dAVF). An 84-year-old woman had a fever and cerebral edema and was initially treated for encephalitis. A review of her magnetic resonance imaging findings revealed abnormal blood flow signals. After cerebral angiography, the patient was finally diagnosed with left transverse-sigmoid sinus dAVF. The present case showed that dAVF can also present with an acute onset and a fever, mimicking acute encephalitis. Because the treatments for encephalitis and dAVF differ greatly, the possibility of dAVF should also be considered when diagnosing encephalitis.

Brain Abnormalities in Becker Muscular Dystrophy: Evaluation by Voxel-Based DTI and Morphometric Analysis.

BACKGROUND AND PURPOSE: Although various neuropsychological problems in Becker muscular dystrophy have attracted attention, there have been few related neuroimaging studies. We investigated brain abnormalities in patients with Becker muscular dystrophy using 3D T1WI and DTI. MATERIALS AND METHODS: MR images were obtained for 30 male patients and 30 age-matched healthy male controls. We classified patients into Dp140+ and Dp140- subgroups based on their predicted dystrophin Dp140 isoform expression and performed voxel-based comparisons of gray and white matter volumes and DTI metrics among the patients, patient subgroups, and controls. ROI-based DTI analyses were also performed. RESULTS: Significantly decreased fractional anisotropy was observed in the left planum temporale and right superior parietal lobule compared between the Becker muscular dystrophy and control groups. In the Dp140- subgroup, decreased fractional anisotropy was observed in the left planum temporale, but no significant changes were seen in the Dp140+ subgroup. The ROI-based analysis obtained the same results. No significant differences were evident in the gray or white matter volumes or the DTI metrics other than fractional anisotropy between the groups. CONCLUSIONS: A DTI metric analysis is useful to detect white-matter microstructural abnormalities in Becker muscular dystrophy that may be affected by the Dp140 isoform expression.

Brain structural changes in alternating hemiplegia of childhood using single-case voxel-based morphometry analysis.

BACKGROUND AND PURPOSE: Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by ATP1A3 mutations. Using voxel-based morphometry (VBM) analysis, we compared an AHC patient cohort with controls. Additionally, with single-case VBM analysis, we assessed the associations between clinical severity and brain volume in patients with AHC. MATERIALS AND METHODS: To investigate structural brain changes in gray matter (GM) and white matter (WM) volumes between 9 patients with AHC and 20 age-matched controls, VBM analysis was performed using three-dimensional T1-weighted magnetic resonance imaging. Single-case VBM analysis was also performed on nine patients with AHC to investigate the associations between the respective volumes of GM/WM differences and the motor level, cognitive level, and status epilepticus severity in patients with AHC. RESULTS: Compared with controls, patients with AHC showed significant GM volume reductions in both hippocampi and diffuse cerebellum, and there were WM reductions in both cerebral hemispheres. In patients with AHC, cases with more motor dysfunction, the less GM/WM volume of cerebellum was shown. Three of the six cases with cognitive dysfunction showed a clear GM volume reduction in the insulae. Five of the six cases with status epilepticus showed the GM volume reduction in hippocampi. One case had severe status epilepticus without motor dysfunction and showed no cerebellar atrophy. CONCLUSION: With single-case VBM analysis, we could show the association between region-specific changes in brain volume and the severity of various clinical symptoms even in a small sample of subjects.

Double inversion recovery MRI of subcortical band heterotopia and its variations.

BACKGROUND AND PURPOSE: Subcortical band heterotopia (SBH) is a malformation of cortical development diagnosed via MRI. Currently, patients with SBH are classified according to Di Donato's classification. We aimed to show a variation of SBH and the usefulness of double inversion recovery (DIR) images. METHODS: We retrospectively reviewed the MRI findings of 28 patients with SBH. The patients were classified according to Donato's classification by using conventional MR images, and their DIR findings were reviewed. RESULTS: Of 28 patients, 20 were grade 1 and 8 were grade 2 according to Di Donato's classification. In 15 of 28 patients, the following four types of atypical MRI findings were detected: asymmetry distribution (four cases), coexistence of thin and thick SBH (five cases), and DIR faint abnormal signal intensity in subcortical white matter (five cases) and in deep white matter (five cases). The latter two types were detected on DIR alone and have not been reported. Additionally, these were identified only in the mild group (Di Donato's classification 1-1 or 1-2). CONCLUSION: DIR is a useful MRI sequence for detecting faint white matter signal abnormalities, and it can aid in the accurate classification of SBH and identification of its variations, which may reflect the pathology of SBH.

Free-water-corrected diffusion and adrenergic/muscarinic antibodies in myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND AND PURPOSE: Free-water-corrected diffusion tensor imaging (FW-DTI), a new analysis method for diffusion MRI, can indicate neuroinflammation and degeneration. There is increasing evidence of autoimmune etiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We used FW-DTI and conventional DTI to investigate microstructural brain changes related to autoantibody titers in patients with ME/CFS. METHODS: We prospectively examined 58 consecutive right-handed ME/CFS patients who underwent both brain MRI including FW-DTI and a blood analysis of autoantibody titers against ß1 adrenergic receptor (ß1 AdR-Ab), ß2 AdR-Ab, M3 acetylcholine receptor (M3 AchR-Ab), and M4 AchR-Ab. We investigated the correlations between these four autoantibody titers and three FW-DTI indices-free water (FW), FW-corrected fractional anisotropy (FAt), and FW-corrected mean diffusivity-as well as two conventional DTI indices-fractional anisotropy (FA) and mean diffusivity. The patients' age and gender were considered as nuisance covariates. We also evaluated the correlations between the FW-DTI indices and the performance status and disease duration. RESULTS: Significant negative correlations between the serum levels of several autoantibody titers and DTI indices were identified, mainly in the right frontal operculum. The disease duration showed significant negative correlations with both FAt and FA in the right frontal operculum. The changes in the FW-corrected DTI indices were observed over a wider extent compared to the conventional DTI indices. CONCLUSIONS: These results demonstrate the value of using DTI to assess the microstructure of ME/CFS. The abnormalities of right frontal operculum may be a diagnostic marker for ME/CFS.

Age and Sex-Related Effects on Single-Subject Gray Matter Networks in Healthy Participants.

Recent developments in image analysis have enabled an individual's brain network to be evaluated and brain age to be predicted from gray matter images. Our study aimed to investigate the effects of age and sex on single-subject gray matter networks using a large sample of healthy participants. We recruited 812 healthy individuals (59.3 ± 14.0 years, 407 females, and 405 males) who underwent three-dimensional T1-weighted magnetic resonance imaging. Similarity-based gray matter networks were constructed, and the following network properties were calculated: normalized clustering, normalized path length, and small-world coefficients. The predicted brain age was computed using a support-vector regression model. We evaluated the network alterations related to age and sex. Additionally, we examined the correlations between the network properties and predicted brain age and compared them with the correlations between the network properties and chronological age. The brain network retained efficient small-world properties regardless of age; however, reduced small-world properties were observed with advancing age. Although women exhibited higher network properties than men and similar age-related network declines as men in the subjects aged < 70 years, faster age-related network declines were observed in women, leading to no differences in sex among the participants aged ≥ 70 years. Brain age correlated well with network properties compared to chronological age in participants aged ≥ 70 years. Although the brain network retained small-world properties, it moved towards randomized networks with aging. Faster age-related network disruptions in women were observed than in men among the elderly. Our findings provide new insights into network alterations underlying aging.

Imaging findings of lesions in the middle and posterior mediastinum.

Lesions in the middle and posterior mediastinum are relatively rare, but there are some useful radiological clues that can be used to diagnose them precisely. It is useful to determine the affected mediastinal compartment and the locations of the main thoracic nerves on medical images for diagnosing such mediastinal lesions. Neurogenic tumors can occur in the middle mediastinum, although they generally arise as posterior mediastinal tumors. Based on the above considerations, we review various characteristic imaging findings of middle and posterior mediastinal lesions, and their differential diagnoses.

Evaluation of Thin-slice Coronal Single-shot Turbo Spin-echo Diffusion-weighted Imaging of the Hand: A Comparison with Conventional Echo-planar Diffusion-weighted Imaging.

We prospectively evaluated thin-slice coronal turbo spin-echo (TSE) diffusion-weighted imaging (DWI) covering a larger area with the recently-developed techniques on a 3T MRI scanner, compared with echo-planar imaging (EPI)-DWI in patients undergoing routine hand MRI. Visual score assessment and apparent diffusion coefficient (ADC) measurement were performed for patients with suspected hand tumors. TSE-DWI was superior to EPI-DWI, with less image distortion. The visual score and ADC comparison assessments proved that the image noise of TSE-DWI was acceptable.

Bronchial arterial embolization using a gelatin sponge for hemoptysis from pulmonary aspergilloma: comparison with other pulmonary diseases.

PURPOSE: To evaluate the clinical outcomes of bronchial artery embolization (BAE) using a gelatin sponge for hemoptysis from pulmonary aspergilloma and compare them with treatment outcomes for hemoptysis from other diseases. METHODS: Fifty-two patients underwent BAE using a gelatin sponge. The etiology of hemoptysis was pulmonary aspergilloma in 8 (PA group) and other diseases in 44 (control group). The technical success rate, clinical success rate, hemoptysis-free rate, and complication rate were compared between the PA group and control group. Technical success was defined as the complete cessation of the targeted feeding artery as confirmed by digital subtraction angiography, and clinical success as the cessation of hemoptysis within 24 h of BAE. Recurrent hemoptysis was defined as a single or multiple episodes of hemoptysis causing > 30 ml of bleeding per day. RESULTS: Technical and clinical success rates were 100% in both groups. Hemoptysis-free rates were 85% at 6 months and 72% at 12-60 months in the control group, and 38% at 6-12 months and 25% thereafter in the PA group (P = 0.0009). No complications were observed following BAE in any case in the two groups. CONCLUSION: BAE using a gelatin sponge may not be effective for hemoptysis from pulmonary aspergilloma.

Differentiation of Kawasaki Disease From Other Causes of Fever and Cervical Lymphadenopathy: A Diagnostic Scoring System Using Contrast-Enhanced CT.

OBJECTIVE: The purpose of this study is to determine the characteristic findings of contrast-enhanced CT (CECT) of the neck in patients with Kawasaki disease (KD) and to develop a diagnostic scoring system to facilitate the diagnosis of KD versus other causes of fever and cervical lymphadenopathy. MATERIALS AND METHODS: Two blinded radiologists evaluated CECT images of 37 patients with KD and 92 patients without KD who had febrile cervical lymphadenopathy, first independently and then in consensus. Significant findings in CECT images were evaluated through cervical edema and lymph node scores. CT attenuation of the nodal low-attenuation area and its ratio to the CT attenuation of the trapezius muscle were measured. On the basis of these indexes, a diagnostic scoring system was developed to differentiate between patients with and without KD. Its diagnostic performance was determined using ROC curve analysis. RESULTS: Retropharyngeal edema, lateral cervical edema, nasopharyngeal wall edema, level IIA lymphadenopathy, and retropharyngeal lymphadenopathy were more common in patients with KD than in patients without KD (p < 0.001, < 0.001, < 0.001, 0.003, and 0.028, respectively). Level VB lymphadenopathy was more common in patients without KD (p = 0.013), and the presence of nodal low-attenuation areas with lower attenuation indexes (attenuation of nodal low-attenuation area ≤ 50 HU, or ratio of attenuation of nodal low-attenuation area to trapezius muscle attenuation ≤ 0.7) was specific to patients without KD. In cases of higher attenuation indexes and cervical edema and lymph node scores of 4 or higher, sensitivity, specificity, and accuracy of the diagnostic scoring system were 86% (32/37), 86% (79/92), and 86% (111/129), respectively, for diagnosing KD. CONCLUSION: The proposed diagnostic scoring system was useful in differentiating between patients with and without KD.

Visualization of the Spinal Artery by CT During Embolization for Pulmonary Artery Pseudoaneurysm.

BACKGROUND: Spinal artery ischemia is a rare but serious complication of embolization for treatment of hemoptysis. When the spinal artery is visualized at angiography, embolization should not be performed. However, it has been reported that spinal artery feeders are not visible on angiography in patients with developing spinal infarction. CASE REPORT: A 70-year-old man with a history of pulmonary aspergillosis had hemoptysis and underwent contrast-enhanced CT, revealing a pulmonary artery pseudoaneurysm (PAP) in the left upper lobe. Systemic angiography from the fifth left intercostal artery showed the PAP at the distal site, but the access route to the PAP was very tortuous and long. Although the spinal branch could not be observed with that angiography, CT during angiography was performed, and it visualized the posterior spinal artery obviously. Thus, the artery distal and proximal to the PAP was then successfully coil-embolized from the pulmonary artery. CONCLUSIONS: CT during angiography may be useful to confirm the presence of the spinal artery for treatment of hemoptysis by embolization.

The variations of the middle colic vein tributaries: depiction by three-dimensional CT angiography.

OBJECTIVE: Laparoscopic transverse colectomy is challenging owing to technical difficulties in identifying an adequate dissection plane, ligating and dissecting lymph nodes around the middle colic vessels. One of the reasons for the technical difficulties is the complex relationship between the middle colic vein (MCV) and its tributary. So, defining the venous anatomy around the MCV before laparoscopic surgery seems important to avoid massive bleeding. The purpose of this study was to evaluate the depiction rate and variation of the MCV and its tributaries on three-dimensional CT angiography (3DCTA). METHODS: This study included 331 patients (203 males and 128 females) scheduled for laparoscopic surgery between June 2010 and April 2012. Most of the patients had gastric or colorectal cancer. Patients who needed emergency surgeries for obstruction or perforation were excluded. 3DCTA with an i.v. contrast medium was performed immediately following the administration of effervescent granules or room air insufflation. We assessed variations of the MCV tributaries using transaxial, multiplanar reconstructed images and volume-rendering images. RESULTS: The MCV could be identified in all patients. The MCVs drained into the superior mesenteric vein in 62.5% of patients, gastrocolic trunk of Henle in 29.3% of patients, inferior mesenteric vein in 4.8% of patients, splenic vein in 2.7% of patients and jejunal vein in 0.6% of patients. CONCLUSION: 3DCTA is useful in evaluating the anatomic variants of the MCV in pre-operative planning for laparoscopic surgery. ADVANCES IN KNOWLEDGE: Use of 3DCTA for the recognition of the anatomic complexity around the MCV and its tributary plays an important role in pre-operative planning for optimal patient outcome.

Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells.

The use of dendritic cells (DC) to prime tumor-associated antigen-specific T-cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSC) require a large number of PSCs at the start of the differentiation culture. In this study, we generated mouse proliferating myeloid cells (pMC) as a source of antigen-presenting cells (APC) using lentivirus-mediated transduction of the c-Myc gene into mouse PSC-derived myeloid cells. The pMCs could propagate almost indefinitely in a cytokine-dependent manner, while retaining their potential to differentiate into functional APCs. After treatment with IL4 plus GM-CSF, the pMCs showed impaired proliferation and differentiated into immature DC-like cells (pMC-DC) expressing low levels of major histocompatibility complex (MHC)-I, MHC-II, CD40, CD80, and CD86. In addition, exposure to maturation stimuli induced the production of TNFα and IL12p70, and enhanced the expression of MHC-II, CD40, and CD86, which is thus suggestive of typical DC maturation. Similar to bone marrow-derived DCs, they stimulated a primary mixed lymphocyte reaction. Furthermore, the in vivo transfer of pMC-DCs pulsed with H-2K(b)-restricted OVA257-264 peptide primed OVA-specific cytotoxic T cells and elicited protection in mice against challenge with OVA-expressing melanoma. Overall, myeloid cells exhibiting cytokine-dependent proliferation and DC-like differentiation may be used to address issues associated with the preparation of DCs.

An HLA-modified ovarian cancer cell line induced CTL responses specific to an epitope derived from claudin-1 presented by HLA-A*24:02 molecules.

In an attempt to induce cytotoxic T lymphocytes (CTLs) that react to ovarian cancer cells, we isolated a CTL clone that specifically recognizes claudin-1 in an HLA-A*24:02-restricted manner. Naïve CD8(+) T lymphocytes were obtained from a healthy adult donor and stimulated twice in vitro with HLA-modified TOV21G cells that were originally derived from an ovarian clear-cell carcinoma line. The TOV21G modification involved RNAi-mediated gene silencing of intrinsic HLA molecules and lentiviral transduction of a synonymously mutated HLA-A*24:02. Then, cDNA library construction using mRNA extracted from the parental TOV21G cells and subsequent expression cloning were conducted. These experiments revealed that a CTL clone obtained from the bulk culture recognized a minimal epitope peptide RYEFGQALF, which was derived from an autoantigen claudin-1 presented by HLA-A*24:02 molecules. This clone exhibited cytolytic activities against three ovarian cancer cell lines and normal bronchial epithelial cells in an HLA-A*24:02-restricted manner. Our data indicate that HLA-modified cancer cells can be used as an artificial antigen-presenting cell to generate antigen-specific CTLs in a manner restricted by an HLA allele of interest.

Zoledronate sensitizes neuroblastoma-derived tumor-initiating cells to cytolysis mediated by human γδ T cells.

Neuroblastoma is the most common extracranial solid tumor in children that is refractory to intensive multimodal therapy. In particular, tumor-initiating cells (TICs) derived from neuroblastoma are believed responsible for tumor formation and resistance to the conventional therapy; an optimal strategy therefore should target this population. Technically, TICs can be enriched from neuroblastoma-derived spheres when the tumor cells are cultured in a serum-free medium supplemented with certain growth factors. Recently, a line of evidence has suggested antitumor potential of Vγ9Vδ2 T cells (γδ T cells), a T-cell population that recognizes and kills target cells independent of surface HLA expressions. Furthermore, a mevalonate pathway inhibitor, zoledronate, has been reported to enhance cytolytic activity of γδ T cells. On the basis of these findings, we hypothesized that zoledronate would sensitize neuroblastoma TICs to γδ T-cell-mediated cytolysis and promote therapeutic efficacy against neuroblastoma. In the current study, we show that zoledronate efficiently sensitizes both neuroblastoma-derived adherent cells and sphere-forming cells to γδ T-cell-mediated cytolysis. Subsequently, in vitro colony formation inhibition assay and in vivo animal studies reveal that the presence of γδ T cells decelerates outgrowth of neuroblastoma TICs. We finally show that addition of interleukin-15 and/or interleukin-18 in culture enhances the cytolytic activity of γδ T cells. On the basis of these data, we conclude that ex vivo expanded γδ T cells are a promising tool for antineuroblastoma immunotherapy with options for further improvement.