A 10-year longitudinal study of deep white matter lesions on magnetic resonance imaging.

PURPOSE: Deep white matter lesions (DWMLs), T2 high-intensity areas in the subcortical white matter on magnetic resonance imaging (MRI), are a clinical phenotype of cerebral small vessel disease. Factors such as age and hypertension have been reported to significantly contribute to the presence and severity of DWMLs in cross-sectional studies. We herein report a 10-year longitudinal study on DWMLs in elderly Japanese subjects to reveal the clinical variables contributing to the progression of DWMLs. METHODS: A total of 469 Japanese subjects were invited to participate in the study. Of the participants at baseline, 259 subjects completed the revisit MRI study 10 years later. In those 259 subjects, we evaluated the correlation between the progression of DWMLs and clinical variables, such as the gender, age, and overt vascular risk factors. To clarify the role of hypertension, 200 subjects with grade 1 DWMLs at baseline were categorized into three groups according to their status of hypertension and its treatment. RESULTS: Of the 200 subjects with grade 1 DWMLs, 47 subjects (23.5%) showed progression of DWMLs (progression group). In the progression group, the percentage of subjects with hypertension and the systolic blood pressure values were higher than in the non-progression group. In addition, subjects ≥ 60 years old at baseline tended to show deterioration of DWMLs in the group with hypertension without antihypertensive treatment. CONCLUSION: The results of this 10-year longitudinal study imply a positive correlation between long-standing hypertension and the progression of DWMLs.

Radiologic-pathologic association of tumor-like lesions with inflammation in cerebral white matter: Comparison of two cases with distinct clinical outcomes.

Here, we report two cases showing tumor-like white matter lesions; one case was diagnosed as having inflammatory disease, and the other was diagnosed as having astrocytoma. Their outcomes were completely distinct despite similar pathology. Prior to biopsy, perfusion computed tomography (CT) and magnetic resonance imaging (MRI) were conducted. The two mass-forming lesions were distinct in edema level and vascularity patterns on CT and MRI. However, pathological examination of brain biopsy specimens revealed commonalities, including (1) proliferation of glial cells, (2) perivascular lymphocytic infiltration, and (3) appearance of numerous macrophages. Although atypical astrocytes proliferated in both cases, nuclear atypia was more distinct in case 2 than in case 1. The immunohistochemical results were the same for both cases: isocitrate dehydrogenase 1 (IDH1) R132H mutation was negative, and alpha thalassaemia mental retardation X-linked (ATRX) was retained. Faint immunoreactivity for p53 was observed in a few glial cells, and Ki-67 immunoreactive cells were markedly reduced in numbers (< 1%). Inflammatory reactions were evident in both cases: T cells dominantly infiltrated over B cells in the perivascular area in case 1, whereas both T and B cells infiltrated in case 2. Molecular analysis revealed wild-type IDH1 and IDH2 in both cases. However, a telomerase reverse transcriptase (TERT) sequence mutation was detected in case 2 but not in case 1. Eventually, case 1 was diagnosed as having inflammatory lesions, whereas case 2 was diagnosed as having diffuse astrocytoma associated with inflammatory reactions. The prognosis was favorable for case 1, whereas case 2 died 10 months following biopsy. These data indicated the diagnostic value of molecular analysis, for example, a TERT mutation, in association with the radiological findings. Although in case 2, histopathological evidence did not suggest high-grade glioma, the case met the new diagnostic criteria: "diffuse astrocytic glioma, IDH wild-type, with molecular features of glioblastoma, World Health Organization (WHO) grade IV," according to cIMPACT-NOW, update 3. Thus, interdisciplinary approaches are essential for accurate diagnosis of newly categorized white matter diseases.

Pineal volume reduction in patients with mild cognitive impairment who converted to Alzheimer's disease.

AIM: Pineal parenchymal volume (PPV) reduction is one of the predisposing factors for Alzheimer's disease (AD). Therefore, PPV could be used as a predictor of developing AD in clinical settings. We investigated whether PPV in patients with mild cognitive impairment (MCI) was correlated with conversion of these patients to AD. METHODS: A total of 237 patients with MCI underwent brain magnetic resonance imaging. A two-sample t-test was used to compare PPV at baseline in MCI patients who converted to AD (MCI-C) with those who did not convert (MCI-NC). Logistic regression analysis with forced entry was used to identify predictors of AD, with variables of PPV, age, sex, education, APOE-ε4 alleles, Mini Mental State Examination score, and total intracranial volume at baseline. Two-way repeated-measures analysis of variance was conducted to compare PPV at baseline and at the last examination in the MCI-C and MCI-NC groups. RESULTS: PPV in the MCI-C group was significantly lower than that in the MCI-NC group. In logistic regression analysis, two independent predictors of AD were identified: Mini Mental State Examination and PPV. Two-way repeated-measures analysis of variance revealed a significant group effect, but no time effect. CONCLUSION: The pineal volume is a predictor of AD conversion, and pineal volume reduction in AD starts early when patients are still in the MCI stage. Thus, pineal volume reduction might be useful as a predictor of developing AD in clinical settings.

Mapping the critical gestational age at birth that alters brain development in preterm-born infants using multi-modal MRI.

Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model-the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the "critical" GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth.

Probabilistic maps of the white matter tracts with known associated functions on the neonatal brain atlas: Application to evaluate longitudinal developmental trajectories in term-born and preterm-born infants.

Diffusion tensor imaging (DTI) has been widely used to investigate the development of the neonatal and infant brain, and deviations related to various diseases or medical conditions like preterm birth. In this study, we created a probabilistic map of fiber pathways with known associated functions, on a published neonatal multimodal atlas. The pathways-of-interest include the superficial white matter (SWM) fibers just beneath the specific cytoarchitectonically defined cortical areas, which were difficult to evaluate with existing DTI analysis methods. The Jülich cytoarchitectonic atlas was applied to define cortical areas related to specific brain functions, and the Dynamic Programming (DP) method was applied to delineate the white matter pathways traversing through the SWM. Probabilistic maps were created for pathways related to motor, somatosensory, auditory, visual, and limbic functions, as well as major white matter tracts, such as the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle, by delineating these structures in eleven healthy term-born neonates. In order to characterize maturation-related changes in diffusivity measures of these pathways, the probabilistic maps were then applied to DTIs of 49 healthy infants who were longitudinally scanned at three time-points, approximately five weeks apart. First, we investigated the normal developmental pattern based on 19 term-born infants. Next, we analyzed 30 preterm-born infants to identify developmental patterns related to preterm birth. Last, we investigated the difference in diffusion measures between these groups to evaluate the effects of preterm birth on the development of these functional pathways. Term-born and preterm-born infants both demonstrated a time-dependent decrease in diffusivity, indicating postnatal maturation in these pathways, with laterality seen in the corticospinal tract and the optic radiation. The comparison between term- and preterm-born infants indicated higher diffusivity in the preterm-born infants than in the term-born infants in three of these pathways: the body of the corpus callosum; the left inferior longitudinal fasciculus; and the pathway connecting the left primary/secondary visual cortices and the motion-sensitive area in the occipitotemporal visual cortex (V5/MT+). Probabilistic maps provided an opportunity to investigate developmental changes of each white matter pathway. Whether alterations in white matter pathways can predict functional outcomes will be further investigated in a follow-up study.

A case of testicular seminoma in persistent Mullerian duct syndrome with transverse testicular ectopia.

We present a rare case of testicular seminoma in persistent Mullerian duct syndrome (PMDS) with transverse testicular ectopia (TTE). A 42-year-old man noticed scrotal swelling a few weeks earlier and underwent magnetic resonance imaging (MRI) on suspicion of testicular tumor. MRI revealed a normal left testis on the left side of the left scrotum and a heterogeneous mass on the right side within the left scrotum. No right testis was found in the right scrotum. A blind-ending tubular structure with thickened wall showed a three-layer appearance on T2-weighted imaging and extended from the prostate through the left inguinal canal to the left scrotum. Findings during surgery suggested right testicular tumor associated with right TTE. The histopathological and immunohistochemical diagnoses of the testicular tumor and blind-ending tubular structure were seminoma and persistent Mullerian duct, respectively. Testicular tumor in PMDS with TTE is rare but may possess a characteristic appearance on imaging. Proper knowledge of these diseases will allow correct preoperative diagnosis.

Brain core temperature of patients with mild traumatic brain injury as assessed by DWI-thermometry.

INTRODUCTION: The aim of this study was to assess the brain core temperature of patients with mild traumatic brain injury (mTBI) using a noninvasive temperature measurement technique based on the diffusion coefficient of the cerebrospinal fluid. METHODS: This retrospective study used the data collected from April 2008 to June 2011. The patient group comprised 20 patients with a Glasgow Coma Scale score of 14 or 15 who underwent magnetic resonance imaging within 30 days after head trauma. The normal control group comprised 14 subjects who volunteered for a brain checkup (known in Japan as "brain dock"). We compared lateral ventricular (LV) temperature between patient and control groups. Follow-up studies were performed for four patients. RESULTS: LV temperature measurements were successfully performed for both patients and controls. Mean (±standard deviation) measured LV temperature was 36.9 ± 1.5 °C in patients, 38.7 ± 1.8 °C in follow-ups, and 37.9 ± 1.2 °C in controls, showing a significant difference between patients and controls (P = 0.017). However, no significant difference was evident between patients and follow-ups (P = 0.595) or between follow-ups and controls (P = 0.465). CONCLUSIONS: A reduction in brain core temperature was observed in patients with mTBI, possibly due to a global decrease in metabolism.

Intracranial calcifications associated with factors related and unrelated to atherosclerosis in older people: A community dwelling cohort study.

The cause of intracranial calcification is not fully understood. The aim of the current study was to identify factors associated with intracranial calcification and to determine whether these factors differ in calcification of different sites. A total of 404 community-dwelling people aged 65 or older were included in the study. All subjects underwent brain computed tomography (CT), blood tests, and a Mini-Mental State Examination (MMSE). Intracranial calcifications were scored using CT. Stepwise regression analysis was performed to examine factors associated with intracranial calcification, with each calcification score used as a dependent variable. Independent variables included age, gender, hemoglobin A1c (HbA1c), dyslipidemia, estimated glomerular filtration rate (eGFR), blood pressure, body mass index (BMI), smoking, serum iron, ferritin, and intact parathyroid hormone (PTH). Stepwise regression analysis detected male gender as a predictor of pineal gland calcification and intact PTH as a predictor of basal ganglia calcification. Age and lifestyle diseases were identified as predictors of calcification of the falx cerebri, internal carotid arteries, and vertebral arteries. These results indicate that the mechanisms of calcifications of the pineal gland and basal ganglia might differ from that of artery calcification, and that causes of intracranial calcification might be classified using factors that are and are not related to atherosclerosis.

Detection of early neuronal damage in CADASIL patients by q-space MR imaging.

INTRODUCTION: q-Space imaging is a novel magnetic resonance (MR) technique that enables the assessment of ultrastructural changes of white matter. We hypothesized that this technique would facilitate the assessment of the progressive nature of neuronal damage seen in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: This study was approved by the institutional review board. Seven consecutive adult patients (five men and two women) with the CADASIL gene mutation were studied. Two patients were preclinical cases without overt episodes of stroke. The control group consisted of five normal volunteers. All MR examinations were performed using a 1.5-T whole-body imager. q-Space imaging was performed using a single-shot, echo-planar imaging technique and Δ/δ = 142/17 ms. Gradient magnitudes were increased in nine steps to reach a maximal b value of 10,000 s/mm². Total acquisition time of q-space imaging was 25 min. The ADC maps calculated from the b = 1,000 images were used for comparisons. RESULTS: Both q-space imaging and ADC maps depicted progressive neuronal damage. Early neuronal damage was especially well depicted using q-space imaging, with preferential involvement of the frontal lobes and central gray matters. Later progression was better depicted by b = 1,000 ADC maps at the temporal lobes. Visual assessment of images revealed a trend for occipital lobe sparing, especially on q-space imaging. CONCLUSION: q-Space imaging demonstrated early neuronal damage in a characteristic distribution. Since this method appears to be sensitive to early neuronal damage, it could conceivably aid in monitoring patients in the preclinical stage and may help in assessing the effects of future medical interventions.

[How Useful is Brain MRI for Early Diagnosis of Alzheimer's Disease?]

MR imaging is often used in assessing patients with dementia, including Alzheimer's disease. Assessment is done through quantitative imaging analysis in addition to visual assessment using structural MRI. Advanced MRI techniques, such as diffusion MRI, functional MRI, arterial spin labeling (ASL), and MR spectroscopy, are also potential imaging biomarkers. In this article, we will outline the current status in the early diagnosis of Alzheimer's disease using these techniques.

The role of breast MR imaging in pre-operative determination of invasive disease for ductal carcinoma in situ diagnosed by needle biopsy.

OBJECTIVES: To evaluate whether magnetic resonance (MR) imaging features can predict the presence of occult invasion in cases of biopsy-proven pure ductal carcinoma in situ (DCIS). METHODS: We retrospectively reviewed 92 biopsy-proven pure DCIS in 92 women who underwent MR imaging. The following MR imaging findings were compared between confirmed DCIS and invasive breast cancer (IBC): lesion size, type, morphological and kinetic assessments by ACR BI-RADS MRI, and findings of fat-suppressed T2-weighted (FS-T2W) imaging. RESULTS: Sixty-eight of 92 (74%) were non-mass-like enhancements (NMLE) and 24 were mass lesions on MR imaging. Twenty-one of 68 (31%) NMLE and 13 of 24 (54%) mass lesions were confirmed as IBC. In NMLE lesions, large lesions (P = 0.007) and higher signal intensities (SI) on FS-T2W images (P = 0.032) were significantly associated with IBC. Lesion size remained a significant independent predictor of invasion in multivariate analysis (P = 0.032), and combined with FS-T2W SIs showed slightly higher observer performances (area under the curve, AUC, 0.71) than lesion size alone (AUC 0.68). There were no useful findings that enabled the differentiation of mass-type lesions. CONCLUSIONS: Breast MR imaging is potentially useful to predict the presence of occult invasion in biopsy-proven DCIS with NMLE. KEY POINTS: MR mammography permits more precise lesion assessment including ductal carcinoma in situ A correct diagnosis of occult invasion before treatment is important for clinicians This study showed the potential of MR mammography to diagnose occult invasion Treatment and/or aggressive biopsy can be given with greater confidence MR mammography can lead to more appropriate management of patients.

A tumefactive anti-MOG antibody associated disorder heralding central nervous system B-cell lymphoma: Case report on diagnostic challenge.

We present the case of a 52-year-old woman with right hemiparesis due to a mass lesion in the left parietal white matter and corpus callosum. The lesion was hyperintense on diffusion weighted image and homogenously enhanced with gadolinium on magnetic resonance imaging, and was radiologically indistinguishable with lymphoma. Following progressive aggravation of symptoms, craniotomy for biopsy of the lesion was performed, and it was revealed that the patient had anti-myelin oligodendrocyte glycoprotein-associated disease by histopathological and serological diagnosis. Initial treatment with steroid dramatically improved the symptoms, but they exacerbated again. Then, through cerebrospinal fluid examination, it was revealed that the patient had B-cell lymphoma.

Association Between Cerebral Microbleeds and Circulating Levels of Mid-Regional Pro-Adrenomedullin.

BACKGROUND: Mid-regional pro-adrenomedullin (MR-proADM) is a novel biomarker for cognitive decline based on its association with cerebral small vessel disease (SVD). Cerebral microbleeds (MBs) are characteristic of SVD; however, a direct association between MR-proADM and MBs has not been explored. OBJECTIVE: We aimed to examine whether circulating levels of MR-proADM are associated with the identification of MBs by brain magnetic resonance imaging (MRI) and whether this association could be linked with cognitive impairment. METHODS: In total, 214 participants (mean age: 75.9 years) without history of cerebral infarction or dementia were prospectively enrolled. All participants underwent brain MRI, higher cognitive function testing, blood biochemistry evaluation, lifestyle examination, and blood MR-proADM measurement using a time-resolved amplified cryptate emission technology assay. For between-group comparisons, the participants were divided into two groups according to whether their levels of MR-proADM were normal (< 0.65 nmol/L) or high (≥0.65 nmol/L). RESULTS: The mean MR-proADM level was 0.515±0.127 nmol/L. There were significant between-group differences in age, hypertension, and HbA1c levels (p < 0.05). In the high MR-proADM group, the MR-proADM level was associated with the identification of MBs on brain MR images and indications of mild cognitive impairment (MCI). In participants with ≥3 MBs and MCI, high MR-proADM levels remained a risk factor after multivariate adjustment (OR: 2.94; p < 0.05). CONCLUSION: High levels of MR-proADM may be a surrogate marker for the early detection of cognitive decline associated with the formation of cerebral MBs. This marker would be valuable during routine clinical examinations of geriatric patients.

Incremental value of T2-weighted and diffusion-weighted MRI for prediction of biochemical recurrence after radical prostatectomy in clinically localized prostate cancer.

BACKGROUND: For men with clinically localized prostate cancer and candidates to receive radical prostatectomy (RP) a main concern is a cancer recurrence after treatment. Although previous studies have demonstrated the diagnostic utility of diffusion-weighted imaging (DWI) for prostate cancer, the prognostic value of pretreatment DWI has not been investigated yet. PURPOSE: To investigate the incremental value of MRI-based T staging using DWI and T2-weighted imaging (T2WI) as compared with the clinical parameters in prediction of biochemical recurrence (BCR) after RP for clinically localized prostate cancer. MATERIAL AND METHODS: Sixty MR examinations, obtained before RP between April 2002 and March 2009, were retrospectively reviewed using T2WI alone, DWI alone, or T2WI + DWI for T staging according to the 2002 American Joint Committee on Cancer guidelines. The relationship between MRI stage and BCR was evaluated using Kaplan-Meier survival estimates. Multivariate analysis and receiver operating characteristics (ROC) curve analysis were used to investigate the incremental value over the standard clinical variables in prediction of BCR. RESULTS: As of August 2009, 12 (20%) patients had BCR. Based on T2WI + DWI, both T3a (compared to OC disease) and T2 (compared to T1c) showed significantly higher BCR rates (p=0.047 and 0.025, respectively). Multivariate analysis and area under ROC curve analysis confirmed the additional value of MRI staging to the conventional clinical variables in prediction of BCR. CONCLUSION: The combination of T2WI and DWI on performing pretreatment MRI helped predict BCR after RP in clinically localized prostate cancer.

[The Diagnosis of Cauda Equina Lesion from the Radiological Aspect].

The cauda equina itself is an unsuitable site for radiological diagnostic imaging because the cauda equina is anatomically a small structure, and magnetic resonance imaging is of limited value to accurately detect lesions in this area. Therefore, in addition to the imaging findings of the cauda equina itself, it is necessary to consider findings in the spinal cord and other areas, as well as clinically correlate these data. In this article, we discuss diseases that cause cauda equina disorders and describe the characteristic imaging findings in such cases.

Optimum b value for resolving crossing fibers: a study with standard clinical b value using 1.5-T MR.

INTRODUCTION: We sought to investigate the optimum b value for resolving crossing fiber using high-angular resolution diffusion imaging (HARDI)-based multi-tensor tractography. The study tested the standard b values that are commonly used in the routine clinical setting. METHODS: Ten normal volunteers (five men and five women) with a mean age of 26.3 years (range, 22-32 years) were scanned using a 1.5-T clinical magnetic resonance unit. Single-shot echo-planar imaging was used for diffusion-weighted imaging with a diffusion-sensitizing gradient in 32 orientations. The b values of 700, 1,400, 2,100, and 2,800 s/m(2) were used. Data postprocessing was performed using multi-tensor methods. The depiction of the optic nerves, optic tracts, and decussation of superior cerebellar peduncles were assessed. RESULTS: The depictions of the nerve fibers were independent of the b values tested. CONCLUSION: The depiction of crossing fibers by HARDI-based multi-tensor tractography is not substantially influenced by b values ranging from 700 to 2,800 s/m(2). Thus, the optimum b value within this range may be the lowest one considering the higher signal to noise ratio.

Whole-tumor histogram analysis of DWI and QSI for differentiating between meningioma and schwannoma: a pilot study.

PURPOSE: To investigate whether whole-tumor histogram analyses of diffusivity measurements derived from q-space imaging (QSI) improves the differentiation between meningioma and schwannoma. MATERIALS AND METHODS: Fifteen extra-axial tumors (11 meningiomas and 4 schwannomas) with MR examinations from April 2011 to May 2013 were included. Three-dimensional regions of interest (ROI) encompassed the whole tumor, including cystic areas. Histogram analyses of mean displacement (MD) derived from QSI and apparent diffusion coefficient (ADC) for the ROI were performed at mean, the five percentiles of MDn and ADCn (n = 5, 25, 50, 75, 95th), kurtosis, and skewness. To determine the diagnostic ability of MDn and ADCn, we also compared the area under the curve (AUC) on receiver operating characteristic (ROC) analysis. RESULTS: Histogram analyses revealed significant differences between meningioma and schwannoma in MD75, ADC25, ADC50, ADC75, and kurtosis of ADC. The ROC analysis of kurtosis of ADC and MD75 resulted in an AUC of 1.0 and 0.96, respectively. There were no significant differences between the AUC of MD75 and that of kurtosis of ADC (p = 0.41). CONCLUSION: The histogram analyses of MD and ADC derived from QSI were both equally useful in differentiating between intracranial meningioma and schwannoma.

Automated Generation of Radiologic Descriptions on Brain Volume Changes From T1-Weighted MR Images: Initial Assessment of Feasibility.

Purpose: To examine the feasibility and potential difficulties of automatically generating radiologic reports (RRs) to articulate the clinically important features of brain magnetic resonance (MR) images. Materials and Methods: We focused on examining brain atrophy by using magnetization-prepared rapid gradient-echo (MPRAGE) images. The technology was based on multi-atlas whole-brain segmentation that identified 283 structures, from which larger superstructures were created to represent the anatomic units most frequently used in RRs. Through two layers of data-reduction filters, based on anatomic and clinical knowledge, raw images (~10 MB) were converted to a few kilobytes of human-readable sentences. The tool was applied to images from 92 patients with memory problems, and the results were compared to RRs independently produced by three experienced radiologists. The mechanisms of disagreement were investigated to understand where machine-human interface succeeded or failed. Results: The automatically generated sentences had low sensitivity (mean: 24.5%) and precision (mean: 24.9%) values; these were significantly lower than the inter-rater sensitivity (mean: 32.7%) and precision (mean: 32.2%) of the radiologists. The causes of disagreement were divided into six error categories: mismatch of anatomic definitions (7.2 ± 9.3%), data-reduction errors (11.4 ± 3.9%), translator errors (3.1 ± 3.1%), difference in the spatial extent of used anatomic terms (8.3 ± 6.7%), segmentation quality (9.8 ± 2.0%), and threshold for sentence-triggering (60.2 ± 16.3%). Conclusion: These error mechanisms raise interesting questions about the potential of automated report generation and the quality of image reading by humans. The most significant discrepancy between the human and automatically generated RRs was caused by the sentence-triggering threshold (the degree of abnormality), which was fixed to z-score >2.0 for the automated generation, while the thresholds by radiologists varied among different anatomical structures.