Elevated Apparent Diffusion Coefficient Research Articles

MRI Reliably Captures Bone Marrow Metrics in Myelofibrosis

Purpose Biopsy remains the clinical standard for evaluating bone marrow of patients with myelofibrosis (MF). However, randomly sampling a small volume of bone marrow, typically from the ilium, fails to capture heterogeneity of disease across anatomic sites. The invasive, painful nature of the procedure limits patient acceptance of repeated biopsies to monitor disease status and response to therapy. Here, we present a non-invasive, MRI technique for evaluating bone marrow in MF. Participants and Methods We analyzed bone marrow of 66 study participants (45 with MF; 15 with essential thrombocytosis or polycythemia vera; and 6 healthy controls). We assessed participant bone marrow across three anatomic sites (vertebral bodies, ilium, and femoral heads), using three quantitative MRI sequences: proton density fat fraction (PDFF) for fat content; apparent diffusion coefficient (ADC) for cellular effect on water mobility; and magnetization transfer (MT) for macromolecular structure and fiber deposition. We correlated these MRI metrics with patient prognosis (dynamic international prognostic scoring system; DIPSS) and iliac biopsy data for cellularity and fibrosis (MF grade). Results Participants with MF had elevated MT ratio (MTR) and ADC and lower PDFF compared to healthy participants. Non-MF MPN participants demonstrated the same trend, though to a lesser extent. Individual MRI metrics correlated strongly across anatomic sites (r pearson from 0.57 to 0.89, p-value < 0.01), with notable heterogeneity both within and among different regions. DIPSS risk groups had limited correlation with MRI metrics. To understand to what extent quantitative MRI biomarkers identify fibrotic marrow, we developed a multivariate logistic regression model to stratify the 45 participants with MF by early fibrosis (MF grades 0-1) and overt fibrosis (MF grades 2-3). Of the seven total anatomy-MRI metric combinations, three had the greatest contributions toward grading marrow fibrosis: PDFF in the vertebral bodies and ilium along with ADC in the ilium. We developed the logistic regression model to predict early and overt fibrosis with these three parameters using a 70%/30% train/test split with 5-fold cross validation. Based on this model, quantitative MRI metrics are associated with the severity of fibrosis in the bone marrow (test set performance: accuracy = 84.6%, sensitivity to predict overt fibrosis = 88.9%, specificity = 75%, area under the receiver operator curve = 0.94). Conclusion Quantitative bone marrow MRI reliably captures relevant metrics of MF bone marrow, including cellularity and fat replacement by fibrosis, and may be useful in clinical drug trials and patient management for MF.

Association between the apparent diffusion coefficient and the preoperative chemotherapy response of patients with locally advanced gastric cancer.

The apparent diffusion coefficient is a parameter measured by magnetic resonance imaging (MRI). Studies in breast cancer and osteosarcoma have shown that the apparent diffusion coefficient has a good correlation with the efficacy of neoadjuvant chemotherapy. However, to date, no studies have evaluated the association between the apparent diffusion coefficient and the preoperative chemotherapy response of patients with locally advanced gastric cancer. The data of 143 patients with locally advanced gastric cancer admitted to Zhejiang Medical and Health Group Quzhou Hospital (Zhejiang Quhua Hospital) from January 2018 to January 2019 were retrospectively collected. All the patients underwent preoperative chemotherapy and dynamic enhanced MRI to analyze the correlation between the apparent diffusion coefficient and preoperative chemotherapy response. Compared to the control group, the apparent diffusion coefficient of the objective remission group was significantly increased [(1.16±0.26) ×10-3 vs. (0.95±0.26) ×10-3 mm2/s, P<0.001]; the rate of the apparent diffusion coefficient >1.095×10-3 mm2/s was significantly increased (61.29% vs. 30.00%, P<0.001). The apparent diffusion coefficient was valuable in predicting objective remission after preoperative chemotherapy in patients with locally advanced gastric cancer, the area under the curve (AUC) was 0.708 [95% confidence interval (CI): 0.621-0.796, P<0.001], the best diagnostic cut-off value was 1.095×10-3 mm2/s, and the sensitivity and specificity were 0.613 and 0.700, respectively. The multivariate logistics regression analysis showed that the apparent diffusion coefficient of >1.095×10-3 mm2/s was associated with the objective response of patients with locally advanced gastric cancer after preoperative chemotherapy [P=0.004, relative risk =3.135 (95% CI: 1.452-6.768)]. The apparent diffusion coefficient was valuable in predicting the non-recurrence of locally advanced gastric cancer patients, and the AUC was 0.647 (95% CI: 0.557-0.738, P=0.003). The apparent diffusion coefficient was also valuable in predicting the postoperative survival of patients with locally advanced gastric cancer, and the AUC was 0.630 (95% CI: 0.537-0.723, P=0.007). The elevated apparent diffusion coefficient was associated with objective remission of the preoperative chemotherapy response and prognosis of patients with locally advanced gastric cancer.

Role of magnetic resonance imaging in differentiating intrasellar cavernous hemangioma and pituitary adenoma: A case report-Decipit frons prima multos.

Cavernous hemangioma represents a rare vascular malformation usually located in the cavernous sinus that could be exceptionally found purely in the intrasellar region. The clinical presentation of intrasellar cavernous hemangioma (ICH), frequently variable and unspecific, poses the patient at risk for misdiagnosis and the clinical consequences of suboptimal treatment. We present a case of ICH and describe the advanced magnetic resonance imaging (MRI) features that should direct toward the clinical suspicion of ICH. An illustrative case of a 61-year-old man complaining of recurrent headaches and diagnosed with a sellar and parasellar lesion was reported and used as a cue to discuss MRI imaging sequences that may aid in the distinction of ICH from pituitary adenoma and other skull base lesions. Heterogeneous enhancement followed by intense homogeneous enhancement at the dynamic contrast-enhanced sequences ("fill-in" phenomenon), absence of blooming signs at the gradient recalled echo (GRE) T2*-weighted and/or susceptibility-weighted imaging (SWI) MRI sequences, and elevated apparent diffusion coefficient (ADC) values usually characterize ICH instead of pituitary adenoma. Advanced MRI imaging plays an invaluable role in the pre-operative characterization of skull base lesions. Although rare, skull base surgeons should be aware of the ICH in the differential diagnosis process in case of the intrasellar lesion, and a tailored MRI examination should be performed to direct the patient toward the safest and optimal treatment.

The Role of Diffusion Tensor Tractography in Assessment of Spondylotic Myelopathy.

IntroductionCervical spondylotic myelopathy (CSM) describes a neurological deficit related to the spinal cord due to the changes in the facet joints and discs of the cervical spine as a result of degeneration. Diagnosis is mainly dependent on imaging. Diffusion tensor tractography (DTT), being a non-invasive technique, shows better sensitivity when compared to the conventional T2WI sequence in the early detection of cervical spondylotic myelopathy (CSM). The objective was to determine the diagnostic accuracy of the apparent diffusion coefficient (ADC) in predicting high T2 signals in CSM.MethodsA prospective observational study was done on 47 subjects aged between 25 and 70 years, referred to the department of radiology with clinical and imaging evidence of CSM in a tertiary care institute in Chennai. Nurick classification system was used to assess severity clinically. Diffusion-weighted imaging and DTT were done with 1.5 Tesla MRI. The primary outcome variable was a high T2 signal. Mean fractional anisotropy (FA) at the stenotic level and ADC value at a stenotic level were considered explanatory variables. The sensitivity, specificity, predictive values, and diagnostic accuracy of the screening test with the decided cut-off values along with their 95% CI were presented. P-value <0.05 was considered statistically significant. SPSS version 22 (IBM Inc., Armonk, New York) was used for statistical analysis.ResultsThe mean age was 48.26 ± 10.28 years. The majority (72.34%) were males, the majority (42.55%) had a Nurick score of two, and 25.53% had a Nurick score of one. Twenty-six (55.32%) reported a high T2 signal, 36 (76.60%) had elevated ADC, and 11 (23.40 %) had no elevated ADC. There was a statistically significant difference in mean FA and ADC values across groups categorized as non-stenotic level and stenotic level (p-value <0.05). The ADC value had a moderately high sensitivity (76.92%) and low specificity (23.81%) in predicting high T2 signals with a diagnostic accuracy of 53.19%.ConclusionDTI parameters at stenotic level (ADC and FA values) in patients with cervical spondylosis help in the early detection of cervical cord compressive myelopathy prior to the appearance of T2 signal changes in conventional MRI, thereby improving clinical outcome and patient management.

Imaging Hallmarks of the Tumor Microenvironment in Glioblastoma Progression.

Glioblastoma progression involves multifaceted changes in vascularity, cellularity, and metabolism. Capturing such complexities of the tumor niche, from the tumor core to the periphery, by magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) methods has translational impact. In human-derived glioblastoma models (U87, U251) we made simultaneous and longitudinal measurements of tumor perfusion (Fp), permeability (Ktrans), and volume fractions of extracellular (ve) and blood (vp) spaces from dynamic contrast enhanced (DCE) MRI, cellularity from apparent diffusion coefficient (ADC) MRI, and extracellular pH (pHe) from an MRSI method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). Spatiotemporal patterns of these parameters during tumorigenesis were unique for each tumor. While U87 tumors grew faster, Fp, Ktrans, and vp increased with tumor growth in both tumors but these trends were more pronounced for U251 tumors. Perfused regions between tumor periphery and core with U87 tumors exhibited higher Fp, but Ktrans of U251 tumors remained lowest at the tumor margin, suggesting primitive vascularization. Tumor growth was uncorrelated with ve, ADC, and pHe. U87 tumors showed correlated regions of reduced ve and lower ADC (higher cellularity), suggesting ongoing proliferation. U251 tumors revealed that the tumor core had higher ve and elevated ADC (lower cellularity), suggesting necrosis development. The entire tumor was uniformly acidic (pHe 6.1-6.8) early and throughout progression, but U251 tumors were more acidic, suggesting lower aerobic glycolysis in U87 tumors. Characterizing these cancer hallmarks with DCE-MRI, ADC-MRI, and BIRDS-MRSI will be useful for exploring tumorigenesis as well as timely therapies targeted to specific vascular and metabolic aspects of the tumor microenvironment.

Letter: Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.

To the Editor: Recently, we read with great interest the article by Quon et al1 regarding the early diffusion magnetic resonance imaging (MRI) changes in normal-appearing brain in pediatric moyamoya disease (MMD). The authors found the significantly elevated apparent diffusion coefficient (ADC) values for MMD children in the representative brain regions could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve (CVR). We really appreciate the interesting observation for their conclusion. Meanwhile, we would like to highlight 3 important questions that it raises. First, in recent years, the researchers of MMD have gradually formed a consensus: prior to the obvious ischemic changes on MRI, the microstructural impairments caused by reduced blood supply had appeared in the brain of MMD patients.2,3 Hypoperfusion and cytotoxic edema have been considered as the major cause of microstructural impairments.4,5 There are 2 different types of cerebral ischemic edema: the early cytotoxic type and the later vasogenic type. When the stimulation of anaerobic metabolism leads to the increase of osmotic pressure of brain tissue, which leads to the swelling of permeable cells, cytotoxic edema occurrs.6 With the development of tissue necrosis and the degradation of basement membrane, the blood-brain barrier is destroyed, and serum protein begins to leak into the brain from the blood, thus further improving the water content of the tissue and a later vasogenic type occurrs.7 However, due to the insensitivity of conventional MRI to the cytotoxic edema, most MMD patients had already suffered serious brain parenchymal damage by the time they receive treatment. In the present study,1 via the high sensitivity of diffusion-weighted imaging in distinguishing cytotoxic and vasogenic edema,8 the authors found the ADC value could precisely differentiate pediatric MMD patients from normal controls in the absence of imaging evidence of ischemic stroke. This observation indicated that it is possible to detect the serious imbalance of energy supplies and demands via the ADC value before the occurrence of irreversible lesions in brain parenchyma in MMD patients, so as to timely implement the intervention measures to obtain the maximum clinical effect. Second, revascularization surgery is considered to be the most effective way to treat MMD. Previous studies have confirmed that the preoperative clinical and hemodynamic changes could indicate the outcomes and complications from revascularization surgery for MMD patients.9,10 However, which severity of the preoperative changes in MMD patients can maximize the benefits from bypass surgery has always puzzled neurosurgeons. Recently, many non-invasive examination methods and indicators, such as CVR,11 ivy sign,12 and cortical hyperintensity belt sign,13 were proposed to reflect the clinical severity of MMD before obvious (usually means serious) changes appear on conventional MRI. The same is true for the ADC value in present study. Third, the authors in present study1 tried to explain a possible relation between the elevated ADC value and the impaired CVR. Although previous studies have observed simultaneous appearance of reduced CVR and elevated ADC in MMD patients, the mechanism remains to be clarified.14 In our opinion, CVR reflects the compensatory ability of cerebral arteries to compensate for the hypoperfusion, and its mechanism may partially due to the vasodilatory stimulation of metabolites like lactate to arteries. Meanwhile, the early cytotoxic edema in MMD patients may also due to the change of metabolism in brain cells during hypoperfusion.6 Therefore, there may not be a direct causal relationship between impaired CVR and elevated ADC, they may be 2 simultaneous results of the same change (hypoperfusion). Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

In Reply: Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.

BACKGROUND Moyamoya disease often leads to ischemic strokes visible on diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI) with subsequent cognitive impairment. In adults with moyamoya, apparent diffusion coefficient (ADC) is correlated with regions of steal phenomenon and executive dysfunction prior to white matter changes. OBJECTIVE To investigate quantitative global diffusion changes in pediatric moyamoya patients prior to explicit structural ischemic damage. METHODS We retrospectively reviewed children (<20 yr old) with moyamoya disease and syndrome who underwent bypass surgery at our institution. We identified 29 children with normal structural preoperative MRI and without findings of cortical infarction or chronic white matter ischemic changes. DWI datasets were used to calculate ADC maps for each subject as well as for 60 age-matched healthy controls. Using an atlas-based approach, the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem were segmented in each DWI dataset and used to calculate regional volumes and ADC values. RESULTS Multivariate analysis of covariance using the regional ADC and volume values as dependent variables and age and gender as covariates revealed a significant difference between the groups (P < .001). Post hoc analysis demonstrated significantly elevated ADC values for children with moyamoya in the cerebral cortex, white matter, caudate, putamen, and nucleus accumbens. No significant volume differences were found. CONCLUSION Prior to having bypass surgery, and in the absence of imaging evidence of ischemic stroke, children with moyamoya exhibit cerebral diffusion changes. These findings could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve.

Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.

Moyamoya disease often leads to ischemic strokes visible on diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI) with subsequent cognitive impairment. In adults with moyamoya, apparent diffusion coefficient (ADC) is correlated with regions of steal phenomenon and executive dysfunction prior to white matter changes. To investigate quantitative global diffusion changes in pediatric moyamoya patients prior to explicit structural ischemic damage. We retrospectively reviewed children (<20 yr old) with moyamoya disease and syndrome who underwent bypass surgery at our institution. We identified 29 children with normal structural preoperative MRI and without findings of cortical infarction or chronic white matter ischemic changes. DWI datasets were used to calculate ADC maps for each subject as well as for 60 age-matched healthy controls. Using an atlas-based approach, the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem were segmented in each DWI dataset and used to calculate regional volumes and ADC values. Multivariate analysis of covariance using the regional ADC and volume values as dependent variables and age and gender as covariates revealed a significant difference between the groups (P<.001). Post hoc analysis demonstrated significantly elevated ADC values for children with moyamoya in the cerebral cortex, white matter, caudate, putamen, and nucleus accumbens. No significant volume differences were found. Prior to having bypass surgery, and in the absence of imaging evidence of ischemic stroke, children with moyamoya exhibit cerebral diffusion changes. These findings could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve.

Decorin Expression Is Associated With Diffusion MR Phenotypes in Glioblastoma

Abstract INTRODUCTION Significant evidence from multiple phase II trials have suggested diffusion-weighted imaging estimates of apparent diffusion coefficient (ADC) are a predictive imaging biomarker for survival benefit for recurrent glioblastoma when treated with anti-VEGF therapies, including bevacizumab, cediranib, and cabozantinib. Despite this observation, the underlying mechanism linking anti-VEGF therapeutic efficacy with diffusion MR characteristics remains unknown. We hypothesized that a high expression of decorin, a small proteoglycan that has been associated with sequestration of pro-angiogenic signaling as well as reduction in the viscosity of the extracellular environment, may be associated with elevated ADC. METHODS A differential gene expression analysis was carried out in human glioblastoma samples in whom preoperative diffusion imaging was obtained. ADC histogram analysis was carried out to calculate preoperative ADCL values, the average ADC in the lower distribution using a double Gaussian mixed model. The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) databases were queried to identify diffusion imaging and levels of decorin protein expression. Patients with recurrent glioblastoma who undergo resection prospectively had targeted biopsies based on the ADC analysis collected. These samples were stained for decorin and quantified using whole-slide image analysis software. RESULTS Differential gene expression analysis between tumors associated with high and low preoperative ADCL showed that patients with high ADCL had increased decorin gene expression. Patients from the TCGA database with elevated ADCL had a significantly higher level of decorin gene expression (P = .01). These patients had a survival advantage with a log-rank analysis (P = .002). Patients with preoperative diffusion imaging had multiple targeted intraoperative biopsies stained for decorin. Patients with high ADCL had increased decorin expression on immunohistochemistry (P = .002). CONCLUSION Increased ADCL on diffusion MR imaging is associated with high decorin expression as well as increased survival in glioblastoma. Decorin may play an important role the imaging features on diffusion MR and anti-VEGF treatment efficacy. Decorin expression may serve as a future therapeutic target in patients with favorable diffusion MR characteristics.

Magnetic Resonance Imaging of Uncommon Hepatic Mesenchymal Tumours: Haemangioendothelioma and Angiosarcoma.

Primary Hepatic Epithelioid Haemangioendothelioma (HEHE) and Primary Hepatic Angiosarcoma (PHA) are rare mesenchymal tumours with different malignant potential. Whereas HEHE demonstrates low to intermediate malignant potential, PHA is an aggressive malignancy with poor prognosis. The knowledge of typical imaging features of these lesions may facilitate correct diagnosis; however, the ultimate diagnosis of HEHE and PHA is based on histopathologic examination. The most typical findings helpful in diagnosing HEHE are: Presence of multiple, confluent nodules located at the liver periphery (in young to middle-aged woman), retraction of the liver capsule, marked hyperintensity on T2-weighted images, "target-sign" appearance, progressive centripetal contrast enhancement, and relatively high Apparent Diffusion Coefficient (ADC) values. More than ≥50% of nodules are hyper- or isointense on Hepatobiliary Phase (HBP) images. The imaging features suggestive of PHA are: Occurrence of metastases (lungs, spleen) at the time of diagnosis, presence of a large dominant mass with smaller satellites, heterogeneity and areas of haemorrhage in a dominant mass, progressive contrast enhancement, slightly elevated ADC values as compared to other malignant liver tumours.

Updated Imaging Features of Dysplastic Cerebellar Gangliocytoma

The aim of this study was to perform an updated review of the imaging features of dysplastic cerebellar gangliocytoma (DCG). Imaging findings were retrospectively reviewed in 14 patients with DCG. The analysis included size, location, cyst formation, calcification, intralesional hemorrhage, enhancement pattern, and apparent diffusion coefficient (ADC). In addition to revisiting many well-established imaging features of DCG, enhancement was much more common (64.3%) than previously reported, and small enhancing veins were also frequently encountered within or along the periphery of the lesions (50%). Dysplastic cerebellar gangliocytomas had an elevated ADC compared with normal cerebellum (967.8 ± 115.7 vs 770.4 ± 47.3 × 10 mm/s; P < 0.0001). Enhancement on magnetic resonance imaging within DCG should be an accepted imaging finding rather than being viewed as uncommon or atypical. Dysplastic cerebellar gangliocytomas typically have an elevated ADC compared with normal cerebellum, which may assist in differentiation from other posterior fossa neoplasms.

Airway Microstructure in Idiopathic Pulmonary Fibrosis: Assessment at Hyperpolarized 3He Diffusion-weighted MRI.

Background MRI with inhaled hyperpolarized helium 3 (3He) allows for functional and structural imaging of the lungs. Hyperpolarized gas diffusion-weighted (DW) MRI provides noninvasive and quantitative assessment of microstructural acinar changes in the lungs. Purpose To investigate whether microstructural imaging metrics from in-vivo hyperpolarized 3He DW MRI are sensitive to longitudinal changes in a cohort of participants with idiopathic pulmonary fibrosis (IPF) and to evaluate the reproducibility of these metrics and their correlation with existing clinical measures of IPF disease severity. Materials and Methods In this prospective study, 18 participants with IPF underwent 3He DW MRI at 1.5 T and 11 participants underwent an identical same-day examination for reproducibility assessment. Thirteen participants returned for 6- and 12-month follow-up examinations. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide and forced vital capacity, were performed at each examination. The apparent diffusion coefficient (ADC) and stretched exponential model-derived mean diffusive length scale (LmD) from DW MRI was compared with baseline CT fibrosis scores and pulmonary function tests by using Spearman rank correlation coefficient. Longitudinal changes in DW MRI and pulmonary function test measurements were assessed with Friedman tests and post hoc Dunn test. Results 3He ADC and LmD were reproducible (mean Bland-Altman analysis bias, 0.002 cm2 · sec-1 and -1.5 μm, respectively). Elevated ADC and LmD regions qualitatively corresponded to fibrotic regions at CT. ADC and LmD correlated with diffusing capacity of the lungs for carbon monoxide (respectively: r = -0.56, P = .017; and r = -0.54, P = .02) and CT fibrosis score (respectively: r = 0.71, P = .001; and r = 0.65, P = .003). LmD increased by 12 μm after 12 months (P = .001) whereas mean ADC (P = .17), forced vital capacity (P = .12), and diffusing capacity of the lungs for carbon monoxide (P > .99) were not statistically different between examinations. Conclusion Helium 3 diffusion-weighted MRI-derived mean diffusive length scale demonstrates longitudinal changes in lungs affected by idiopathic pulmonary fibrosis. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Altes and Flors in this issue.

Abstract WP550: Pathophysiology of Acute, Subacute and Chronic Lesions in Stroke: A Radiological-Pathological Analysis

Introduction: The imaging characteristics of ischemic lesions seen on MRI aid in the interpretation of the lesion pathogenesis. Early ischemic lesions are seen on diffusion weighted imaging (DWI) with low apparent diffusion coefficient (ADC), later evolve on T2-FLAIR, develop elevated ADC, then disappear on DWI. Chronic white matter lesions (WML) seen on T2-FLAIR but not DWI may or may not be of ischemic origin. Here we present an MRI targeted pathology approach to better describe in-vivo MRI based on cellular changes. Methods: The brain of a patient was obtained for pathological evaluation early after stroke recurrence. As part of clinical care and study procedures, 3T MRI was obtained at baseline (within 2-hours), multiple follow-up visits, and during second admission. Radiological-pathological methods previously validated in trauma was employed. Whole brain 7T MRI was performed after formalin fixation, and MRI targeted pathology was performed, co-localizing three lesions of different ages based on history and presumed imaging characteristics; i) acute, ii) subacute, and iii) chronic vs WML. Homologous contralateral tissue was used as control. Results: Lesions seen in-vivo were observed in post mortem MRI, and reconfirmed in histology. An example of in-vivo and post-mortem MRI, along with corresponding tissue sections and H&amp;E are shown in figure. Qualitative delineation of the boundaries of the chronic lesion on H&amp;E was challenging. A large number of small vessels with enlarged perivascular spaces dominated. The subacute lesion, was characterized by loss of white mater, infiltration of macrophages, and astrocytosis. The acute lesion had a text-book appearance. Conclusion: Dramatic differences are seen in the volume fraction of free water, which likely a major contributor to the appearance on DWI/ADC and T2 FLAIR. Work continues with immunohistochemistry to better delineate the boundaries of the lesions and cellular morphology relevant to in-vivo MRI.

A Retrospective Study of Predictors of Return to Duty versus Medical Retirement in an Active Duty Military Population with Blast-Related Mild Traumatic Brain Injury.

Traumatic Brain Injury (TBI) has been described as the "signature injury" of the Global War on Terror. Explosive blast TBI has become a leading cause of injury as a result of the widespread use of improvised explosive devices in Iraq and Afghanistan. We present a retrospective cross-sectional study of patients with blast-related mild TBI (mTBI, N = 303) seen at the Intrepid Spirit Concussion Recovery Center at Naval Medical Center Camp Lejeune. The objective was to predict outcomes of return to duty (RTD) vs. medical retirement via medical evaluation board (MEB), based on brain imaging, neuropsychological data, and history of mTBI. The motivation is to inform prognosis and target resources to improve outcomes for service members who are less likely to RTD through the standard treatment program. The RTD was defined operationally as individuals who completed treatment and were not recommended for medical retirement or separation for TBI or related sequelae. Higher scores on the Repeatable Battery for Neuropsychological Status (RBANS) test were associated positively with RTD (p = 0.001). A history of three or more lifetime concussions was associated negatively with RTD, when compared with one concussion (p = 0.04). Elevated apparent diffusion coefficient (ADC) in the anterior corona radiata was associated negatively with RTD (p = 0.04). A logistic regression model was used to classify individuals with RBANS and imaging data (n = 81) as RTD or MEB according to RBANS, ADC, and a history of multiple (≥3) concussions. The RBANS (p = 0.003) and multiple concussions (p = 0.03) were significant terms in the logistic model, but ADC was not (p = 0.27). The area under the receiver operating characteristic curve was 0.77 (95% confidence interval 0.66-0.86). These results suggest cognitive testing and TBI history might be used to identify service members who are more likely to be retired medically from active duty.

Predicting postnatal renal function of prenatally detected posterior urethral valves using fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient determination.

The objective of this study was to evaluate the accuracy of fetal diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) determination to predict postnatal renal function (nadir creatinine at 1 year and eGFR) of men with posterior urethral valves (PUV). Between 2003 and 2014, 11 MRI were performed on fetuses (between 28 and 32weeks) in whom second trimester sonography suggested severe bilateral urinary tract anomalies, suspected of PUV. The ADC of the 11 fetuses ranged from 1.3 to 2.86mm2 s-1 (median=1.79mm2 s-1 , normal range for fetal kidney: 1.1-1.8). Two pregnancies with ADC>2.6mm2 s-1 were interrupted; the autopsy confirmed PUV and Potter syndrome. For the remaining nine babies, the follow-up was 5.4years (0.8-10). Four children with abnormal ADC (1.8-2.3) had chronic kidney disease. The remaining five cases with normal nadir creatinine and eGFR had normal ADC. One case with unilateral elevated ADC had a poor ipsilateral renal function on dimercaptosuccinic acid scan. Here, it seems that diffusion-weighted magnetic resonance imaging with ADC determination could be useful in accurately evaluating fetal kidneys in PUV and predicting renal function. It may be an additional, non-invasive method when biologic and sonographic findings are inconclusive, especially in the case of oligohydramnios. Further studies are needed to confirm our data. © 2017 John Wiley & Sons, Ltd.

Potential diagnostic role of diffusion tensor imaging in early-stage osteonecrosis of the femoral head.

The present study aimed to explore the potential diagnostic role of diffusion tensor magnetic resonance imaging (DTI) in the early stage of modified corticosteroid-induced osteonecrosis of the femoral head (ONFH). A total of 20 beagles were randomly classified (1:1) into either an experimental group (LM), which were intramuscularly injected with lipopolysaccharide (LPS) and methylprednisolone (MPS) on three consecutive days, or control (CON) group, which were injected with saline. Magnetic resonance imaging (MRI) and DTI were performed at pre-induction and 8 and 12 weeks post-induction. Apparent diffusion coefficient (ADC) values in the range of interest in the femoral head were quantified using DTI. Proximal femora were examined for ONFH at 8 and 12 weeks. The results demonstrated that ONFH developed in four beagles at 8 weeks and in six beagles at 12 weeks, whereas no ONFH was detected in the CON group. No abnormalities were detected by MRI and DTI, and no mortality occurred. In beagles with ONFH in the LM group, the ADC values were 4.7±0.2×10-4 and 4.8±0.3×10-4 mm2/sec at 8 and 12 weeks, respectively, which were significantly increased compared with the CON group (2.5±0.3×10-4 and 2.4±0.3×10-4 mm2, respectively) and the LM group without ONFH (2.6±0.4×10-4 and 2.4±0.3×10-4 mm2, respectively) (P<0.05). The results of the present study indicated that intramuscular injection of LPS and MPS may lead to early-stage ONFH in beagles. As such, the detection of locally elevated ADC values in the femoral head may aid in the early diagnosis of ONFH.

The usefulness of diffusion-weighted imaging for differentiating portal vein thrombus from tumour embolus

To investigate the usefulness of diffusion-weighted imaging (DWI) for differentiating bland portal vein thrombus from tumour thrombus. Fifteen patients with clinical comprehensive diagnoses of portal vein thrombus were analysed retrospectively. The thrombus signal intensity on 21 DWI slices and apparent diffusion coefficient (ADC) values were analysed quantitatively. The portal vein thrombus was divided into four types (low/low, high/low, low/high, and high/high) based on the DWI/ADC ratios between the thrombus and liver parenchyma (rDWI and rADC, respectively). Twenty patients with portal vein tumour thrombi were used for comparison as controls. The average ADC value for the bland thrombus was 1.84 ± 0.70 × 10−3 mm2 s−1 (range: 0.46–2.77 × 10−3 mm2 s−1), and was 2.18 ± 0.51 × 10−3 mm2 s−1 (range: 1.39–2.82 × 10−3 mm2 s−1) for the liver parenchyma; the rADC was therefore 0.90 ± 0.45 (range: 0.26–1.86). The tumour thrombi were high/low and high/high type. The average ADC for the tumour thrombus was 1.25 ± 0.26 × 10−3 mm2 s−1 (range: 0.68–1.67 × 10−3 mm2 s−1), and 1.56 ± 0.33 × 10−3 mm2 s−1 (range: 1.11–2.34 × 10−3 mm2 s−1) for the liver parenchyma; the rADC was therefore 0.82 ± 0.16 (range: 0.39–1.08). There was no statistical difference in rADC values and rDWI/rADC classification performance between the bland and tumour thrombi. The ADC difference between portal vein bland and tumour thrombi was statistically significant, but the ADC values of bland thrombi have a wider range, which contains the ADC values of tumour thrombi with a narrower range. The elevated ADC values of the liver parenchyma adjacent to portal vein emboli may be helpful for the diagnosis of bland thrombi.

Pulmonary ventilation and micro-structural findings in congenital diaphragmatic hernia.

With increasing survival of patients with more severe forms of congenital diaphragmatic hernia (CDH) and risk of long-term respiratory morbidity, studies on lung morphology are needed. We used hyperpolarised (3) He MRI and anatomical (1) H MRI in a cohort of young adult CDH patients to image regional lung ventilation and microstructure, focusing on morphological and micro-structural (alveolar) abnormalities. Nine patients with left-sided CDH, born 1975-1993, were studied. Regional ventilation was imaged with hyperpolarised (3) He MRI, and the (3) He apparent diffusion coefficient (ADC) was computed separately for the ipsilateral and contralateral lungs. (1) H MRI was used to image lung anatomy, total lung volume and motion during free-breathing. (3) He MRI showed ventilation abnormalities in six patients, ranging from a single ipsilateral ventilation defect (3 patients) to multiple ventilation defects in both lungs (one patient treated with extra corporeal membrane oxygenation). In eight patients, (3) He ADC values for the ipsilateral lung were significantly higher than those for the contralateral lung. Functional and micro-structural changes persist into adulthood in most CDH patients. Ipsilateral elevated (3) He ADC values are consistent with enlargement of mean dimensions of the confining lung micro-structure at the alveolar level.

Using the apparent diffusion coefficient to identifying MGMT promoter methylation status early in glioblastoma: importance of analytical method.

IntroductionAccurate knowledge of O6-methylguanine methyltransferase (MGMT) gene promoter subtype in patients with glioblastoma (GBM) is important for treatment. However, this test is not always available. Pre-operative diffusion MRI (dMRI) can be used to probe tumour biology using the apparent diffusion coefficient (ADC); however, its ability to act as a surrogate to predict MGMT status has shown mixed results. We investigated whether this was due to variations in the method used to analyse ADC.MethodsWe undertook a retrospective study of 32 patients with GBM who had MGMT status measured. Matching pre-operative MRI data were used to calculate the ADC within contrast enhancing regions of tumour. The relationship between ADC and MGMT was examined using two published ADC methods.ResultsA strong trend between a measure of ‘minimum ADC’ and methylation status was seen. An elevated minimum ADC was more likely in the methylated compared to the unmethylated MGMT group (U = 56, P = 0.0561). In contrast, utilising a two-mixture model histogram approach, a significant reduction in mean measure of the ‘low ADC’ component within the histogram was associated with an MGMT promoter methylation subtype (P < 0.0246).ConclusionThis study shows that within the same patient cohort, the method selected to analyse ADC measures has a significant bearing on the use of that metric as a surrogate marker of MGMT status. Thus for dMRI data to be clinically useful, consistent methods of data analysis need to be established prior to establishing any relationship with genetic or epigenetic profiling.

S120 Hyperpolarised 3HE diffusion MRI and multiple breath inert gas washout in patients with asthma

BackgroundMultiple breath inert gas washout (MBW) is a technique for detecting abnormal ventilation distribution in patients with asthma and other airway diseases. Scond and Sacin are measures of convective-dependent inhomogeneity...