Gadolinium Contrast Enhancement Research Articles

Successful donor engraftment and repair of the blood-brain barrier in cerebral adrenoleukodystrophy

AbstractAdrenoleukodystrophy (ALD) is caused by mutations within the X-linked ABCD1 gene, resulting in the inability to transport acylated very long chain fatty acids (VLCFAs) into the peroxisome for degradation. VLCFAs subsequently accumulate in tissues, including the central nervous system. Up to 40% of boys develop a severe progressive demyelinating form of ALD, cerebral ALD, resulting in regions of demyelination observed on brain magnetic resonance imaging that are associated with a “garland ring” of gadolinium contrast enhancement. Gadolinium enhancement indicates blood-brain barrier (BBB) disruption and an active inflammatory disease process. Only hematopoietic cell transplant (HCT) has been shown to halt neurologic progression, although the mechanism of disease arrest is unknown. We evaluated imaging- and transplant-related biomarkers in 66 males who underwent HCT. In 77% of patients, gadolinium contrast resolved by 60 days post-HCT. We determined that time to neutrophil recovery and extent of donor chimerism correlated significantly with time to contrast resolution post-HCT. Graft failure was associated with a significantly slower rate of contrast resolution (P < .0001). Time to neutrophil recovery remained significant in multivariate analysis with other biomarkers (P = .03). Our data suggest that robust donor myeloid recovery is necessary for timely repair of the BBB.

Repair of the Blood Brain Barrier with Neutrophil Recovery Following HSCT for Cerebral Adrenoleukodystrophy

Introduction Cerebral leukodystrophy is an X-linked peroxisomal disease characterized by mutations in the ABCD1 gene, resulting in the lack of very long chain fatty acid (VLCFA) transport into peroxisomes. Resultant VLCFA build up in the blood and tissues leads to adrenal gland insufficiency in 95% of boys and an inflammatory cerebral demyelinating process in 40% of patients, which is progressive and most often fatal (cALD). A key clinical feature of cALD is disruption of the blood brain barrier (BBB) illustrated by gadolinium (gad) contrast enhancement on brain MRI at diagnosis and as an indicator of active cerebral disease. Only hematopoietic stem cell transplant (HSCT) has been shown to halt cerebral disease progression. After HSCT, gad enhancement resolves in 90% of cases by 100 days post HSCT in our experience. Objective A seminal question in the field is how recovery of donor-derived hematopoiesis relates to BBB repair and gad resolution. Methods We evaluated the pre-HSCT characteristics and 1-year post-HSCT outcomes in 66 boys undergoing marrow or umbilical cord blood HSCT for cALD. Results The median total nucleated cell (TNC) dose was 0.8 × 108 cells/kg and CD34+ cell dose was 1.27 × 106 cells/kg. Pre-HSCT characteristics included: cALD on MRI quantified using the Loes scoring system, neurologic disability using the neurologic function scale (NFS), plasma and cerebral spinal fluid (CSF) chitotriosidase level, and intensity of gadolinium on pre-HSCT MRI (gad score). We found 77% boys had gad resolution by day +28 (early) post-HSCT and 90% had gad resolution by day +100 (later) post-HSCT. Patients with gad resolution by day +60 post-HSCT had lower Loes scores at 1-year (p = 0.008), lower absolute NFS (p = 0.004), and less progression of neurologic symptoms (post-HSCT NFS – pre-HSCT NFS, p = 0.02). Importantly, we found neutrophil recovery occurred at a mean of 16 days in the patients with day +60 gad resolution compared to 20 days in those without gad resolution (p = 0.008). Other factors associated with early gad resolution were: lower Loes score (p = 0.003), lower NFS (p = 0.003), lower plasma chitotriosidase (p = 0.02), lower CSF chitotriosidase (p = 0.02), and lower gad score (p = 0.02). On multivariate analysis, only the day of neutrophil recovery post-HSCT remained significant with p = 0.04). There was no significant difference in cell dose between the groups. In patients with graft failure, day +60 gad resolution occurred in only 8% (n = 18, p = 0.01). Conclusion This is the first study to link neutrophil recovery following HSCT and early repair of the BBB (gadolinium resolution). This is an important observation, as gad resolution is thought to be an indicator of cerebral disease arrest and activity of neuroinflammation. This observation may also serve as a useful biomarker as new therapies for cALD are being developed, including gene therapy and CD34 expansion.

Mitral annular disjunction in mitral valve prolapse: A Cardiac Magnetic Resonance study

Few data exist on cardiac magnetic resonance (CMR) prevalence of mitral annulus disjunction (MAD) in mitral valve prolapse (MVP) and its morphological characteristics. To assess the prevalence of MAD and its consequences on left ventricle (LV) morphology in MVP patients using CMR. 89 patients with MVP (63 women; mean age 64 ± 13) referred for CMR assessment of mitral regurgitation (MR) were evaluated. MVP etiology was either Myxomatous Mitral Valve Disease (MMVP) ( n = 40; 45%) or fibroelastic disease (FED) ( n = 49; 55%). In total, 26/89 (29%) patients underwent injected gadolinium contrast enhancement (GE). MR severity was calculated using the volumetric method with CMR. LV systolic diameter (LVSD), and mitral annulus end systolic (ES) and diastolic (ED) diameters were measured. MAD was defined as a separation between the left atrium-valve junction and the LV posterior free wall, diagnosed by CMR from long axis view in end-systole ( Fig. 1 ). Patients were classified in 2 groups according to presence (MAD+) or absence of MAD (MAD−). MAD was found in 35% (31/89) of MVP patients, measuring 8 ± 4 mm. MAD was more frequent in MMVP (24/40; 60%) than in FED (7/49; 14%; P < 0.0001). Presence of MAD was associated with ventricular arrhythmias (VA) ( P = 0.037), but not with MR severity (regurgitant volume in MAD+ was 47 ± 32 vs. 56 ± 23 ml/beat, P = 0.141). MAD+ showed enlarged basal LVSD (41 ± 9 vs. 37 ± 7 mm, P = 0.014) and mitral annulus, in both ES (49 ± 6 vs. 44 ± 5 mm, P < 0.0001) and ED (48 ± 5 vs. 44 ± 4 mm, P = 0.004). Among the 11/26 patients (42%) with late GE, 83% (5/6) of the patients with LV fibrosis at the level of papillary muscle (PM) had MAD. After adjustment on age and MR severity, MMVP (HR 5.04; 95% CI [1.66–15.31], P = 0.004) and dilated ES mitral annulus diameter (HR 1.17; 95% CI [1.05–1.30], P = 0.005) were independent predictors of MAD ( Table 1 ). MMVP, enlarged LVSD, enlarged mitral annular, VA and PM fibrosis were associated with MAD, independently of MR severity.

Repair of the Blood Brain Barrier and Neutrophil Recovery Following HSCT in Cerebral Adrenoleukodystrophy

▪Cerebral leukodystrophy is an X-linked peroxisomal disease characterized by mutations in the ABCD1 gene, resulting in the lack of very long chain fatty acid (VLCFA) transport into peroxisomes. Resultant VLCFA build up in the blood and tissues leads to adrenal gland insufficiency in 95% of boys and a progressive inflammatory cerebral demyelinating process in 40% of patients, which is progressive and most often fatal (cALD). Only hematopoietic stem cell transplant (HSCT) has been shown to halt cerebral disease progression. A key clinical feature of cALD is disruption of the blood brain barrier (BBB) illustrated by gadolinium (gad) contrast enhancement on brain MRI at diagnosis and as an indicator of “active” cerebral disease. Following successful donor neutrophil recovery after HSCT, gad enhancement resolves in the majority of cases by 100 days post HSCT in our experience. A seminal question in the field is how recovery of donor-derived hematopoiesis relates to BBB repair and gad resolution. We evaluated the pre-HSCT characteristics and 1- year post-HSCT outcomes in 78 boys undergoing marrow or umbilical cord blood HSCT for cALD. The median total nucleated cell (TNC) dose was 0.8 x 108cells/kg and CD34+ cell dose was 1.27 x 106cells/kg. Pre-HSCT characteristics included: cALD on MRI quantitated using the Loes scoring system, neurologic disability using the neurologic function scale (NFS), plasma and cerebral spinal fluid (CSF) chitotriosidase level, and intensity of gadolinium on pre-HSCT MRI (gad score). We found 39 boys (59%) had gad resolution by day +28 (early) post-HSCT and 79% had gad resolution by day +100 (later) post-HSCT. Patients with gad resolution by day +28 post-HSCT had lower Loes scores at 1-year (p = 0.008), lower absolute NFS (p = 0.004), and less progression of neurologic symptoms (post-HSCT NFS - pre-HSCT NFS, p = 0.02). Graft failure had occurred in 13% of patients with early gad resolution and in 40% in those without early gad resolution (Fishers exact test p = 0.01). Interestingly, in patients without graft failure we found neutrophil recovery occurred at a mean of 16 days in the early patients compared to 20 days in those without gad resolution (p = 0.02).Factors associated with early gad resolution were: lower Loes score (p = 0.003), lower NFS (p = 0.003), lower plasma chitotriosidase (p = 0.02), lower CSF chitotriosidase (p = 0.02), day of neutrophil recovery post-HSCT (p = 0.008), and lower gad score (p = 0.02). On multivariate analysis, only the day of neutrophil recovery post-HSCT remained significant with p = 0.04). There was no significant difference in cell dose between the groups. This is the first study to link neutrophil recovery following HSCT and early repair of the BBB (gadolinium resolution). This is an important observation, as gad resolution is thought to be an indicator of cerebral disease arrest and activity of neuroinflammation. This observation may also serve as a useful biomarker as new therapies for cALD are being developed, including gene therapy and CD34 expansion. DisclosuresLund:Magenta Therapeutics: Research Funding. Miller:Sangamo Therapeutics: Employment. Orchard:Magenta Therapeutics: Research Funding.

Sensitivity of orbital magnetic resonance imaging in acute demyelinating optic neuritis

ObjectiveTo determine the sensitivity of orbital magnetic resonance imaging (MRI) in acute demyelinating optic neuritis (ON) in routine clinical practice, and the added value of a dedicated neuroradiology interpretation. DesignRetrospective chart review. ParticipantsPatients with clinically proven ON evaluated between 2004 and 2014 in the University of Michigan neuro-ophthalmology clinics. Inclusion criteria involved visual recovery and orbital MRI completed within 30days of symptom onset and before corticosteroid treatment. MethodsDemographics, clinical examination, and MRI report data (high T2 signal, gadolinium contrast enhancement) were abstracted for each eligible eye. Every MRI was reinterpreted by a neuroradiologist masked to the affected side. Descriptive statistics summarized patient and eye characteristics. Interrater agreement between the neuroradiologist and the radiology report for the radiographic diagnosis of ON was assessed with Cohen's kappa statistic. ResultsOf 92 patients who met all inclusion criteria, 70 (76.1%) were reported to have at least 1 MRI feature consistent with ON. After dedicated review by a neuroradiologist, 77 (83.7%) were determined to have a positive MRI for ON. Agreement between the neuroradiologist and MRI report was moderate (κ = 0.63). Gadolinium enhancement was the most common feature in MRI positive ON (72 [78.3%] of neuroradiology reviewed MRIs; 66 [71.7%] of clinical MRI reports). ConclusionsThe sensitivity of MRI in ON was lower than previously reported and confirms the importance of making a clinical diagnosis of ON without relying on neuroimaging for confirmation. MRI interpretation by a skilled neuroradiologist increased sensitivity, underscoring the complexity of orbital MRI interpretation.

Granular cell tumor of the infundibulum: a systematic review of MR-radiography, pathology, and clinical findings.

Granular cell tumors (GCTs) of the infundibulum are rare in practice and literature, resulting in a lack of evidence-based standard of care. We present two characteristic cases from our institution and perform a systematic review of the existing literature to further elucidate the presentation of this tumor and guide management. A systematic literature search was conducted according to PRISMA guidelines, yielding 42 total individual reported GCTs suitable for evaluation. Available clinical presentation, magnetic resonance imaging (MRI) characteristics, pathology, surgical approaches, and outcomes were charted. We measured frequencies of clinical characteristics and performed an outcome comparison of open versus endoscopic surgical treatment. In this pooled dataset, GCT incidence was higher in females than males (3:1). Clinical presentation peaked in the fourth decade with tumor-related symptoms. MRI appearance was characterized by T1 isointensity (50%) and T2 hypointensity or isointensity (52%) with gadolinium contrast enhancement (74%). Histopathology demonstrated positive staining for PAS, PAS-D, S100, CD68, and TTF1. In a simple uncontrolled analysis, patients who underwent endoscopic surgery experienced more symptom improvement (p = 0.006) and lower incidence of new diabetes insipidus postoperatively (p = 0.047) versus patients who underwent open microsurgery. This first comprehensive review of GCTs of the infundibulum corroborates existing data and adds significant new MR-radiological information to the literature, notably a typical tumor appearance of T1 isointensity, T2 iso- to hypointensity, and gadolinium contrast enhancement. Future prospective studies should be conducted to validate our findings.

DCE-MRI in Human Gliomas: A Surrogate for Assessment of Invasive Hypoxia Marker HIF-1Α Based on MRI-Neuronavigation Stereotactic Biopsies

The purpose of this study was to correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with data from a specific marker of hypoxia, hypoxia-inducible factor 1α (HIF-1α), in human gliomas on a point-to-point basis by using coregistered magnetic resonance imaging and frameless stereotactic biopsies. Thirty-four patients with treatment-naive gliomas underwent DCE, axial T1-weighted, T2-weighted, T2-weighted fluid acquisition of inversion recovery, and three-dimensional T1-weighted brain volume with gadolinium contrast enhancement sequences on a 3.0-T magnetic resonance scanner before stereotactic surgery. Quantitative perfusion indices such as endothelial transfer constant, fractional extravascular extracellular space volume, fractional plasma volume, and reflux rate were measured at corresponding stereotactic biopsy sites. Each sample was considered an independent measurement, and its histology grade was diagnosed. HIF-1α expression was quantified from the point-to-point biopsy tissues. Analyses of receiver operating characteristic curves were done for HIF-1α to discriminate different grades of glioma. To look for correlations between immunohistochemical parameters and DCE indices, Spearman's correlation coefficient was used. Seventy biopsy samples from 34 subjects were included in the analysis. Mean immunoreactivity scores of HIF-1α were 2.75 ± 1.11 for grade II (n = 24), 6.20 ± 2.33 for grade III (n = 20), and 10.46 ± 2.42 for grade IV (n = 26). HIF-1α showed very good-to-excellent accuracy in discriminating grade II from III, III from IV, and II from IV (area under the curve = 0.838, 0.862, and 0.994, respectively). Endothelial transfer constant and fractional extravascular extracellular space volume showed a significantly positive correlation with HIF-1α expression (r = 0.686, P < .001; r = 0.549, P < .001, respectively). Our study demonstrated HIF-1α to be a significant predictor of different grades of gliomas with high sensitivity and specificity. DCE-MRI is a useful, noninvasive imaging tool for quantitative evaluation of HIF-1α, and its parameters may be used as a surrogate for HIF-1α expression.

Sarcoidosis Mimicking Skull Base Meningioma

AbstractSarcoidosis is a systemic disease characterized by granulomatous inflammation. Pulmonary and lymphatic granulomatous involvement are common. We present a rare case report of involvement of the central nervous system affecting the ocular region and mimicking optic nerve sheath meningioma. We report the case of a 79-year-old female patient with progressive visual impairment with an evolution of 4 years. A magnetic resonance imaging scan of the cranium with gadolinium and intense homogeneous contrast enhancement revealed an expansive lesion in the right optic nerve, at the height of the optic canal. The patient was submitted to the neurosurgical approach with lesion biopsy, which showed sarcoidosis of the central nervous system. Due to the rarity of central nervous system involvement, the diagnosis of this pathology may unfortunately be postponed. The present article aims to elucidate this pathology as a differential diagnosis of retro-orbital tumors.

Utilizing 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) to define suspected nonenhancing tumor for radiation therapy planning of glioblastoma

AimThe authors sought to evaluate the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and the presence of suspected nonenhancing tumors compared with standard magnetic resonance imaging (MRI). Methods and materialsPatients with GBM and contrast-enhanced MRI scans showing regions suspicious of nonenhancing tumor underwent postoperative FET-PET before commencing radiation therapy. Two clinical target volumes (CTVs) were created using pre- and postoperative MRI: MRI fluid-attenuated inversion recovery (FLAIR) sequences (CTVFLAIR) and MRI contrast sequences with an expansion on the surgical cavity (CTVSx). FET-PET was used to create biological tumor volumes (BTVs) by encompassing FET-avid regions, forming BTVFLAIR and BTVSx. Volumetric analyses were conducted between CTVs and respective BTVs using Wilcoxon signed-rank tests. The volume increase with addition of FET was analyzed with respect to BTVFLAIR and BTVSx. Presence of focal gadolinium contrast enhancement within previously nonenhancing tumor or within the FET-avid region was noted on MRI scans at 1 and 3 months after radiation therapy. ResultsTwenty-six patients were identified retrospectively from our database, of whom 24 had demonstrable FET uptake. The median CTVFLAIR, CTVSx, BTVFLAIR, and BTVSx were 57.1 mL (range, 1.1-217.4), 83.6 mL (range, 27.2-275.8), 62.8 mL (range, 1.1-307.3), and 94.7 mL (range, 27.2-285.5), respectively. When FET-PET was used, there was a mean increase in volume of 26.8% from CTVFLAIR to BTVFLAIR and 20.6% from CTVSx to BTVSx. A statistically significant difference was noted on Wilcoxon signed-rank test when assessing volumetric change between CTVFLAIR and BTVFLAIR (P < .0001) and CTVSx and BTVSx (P < .0001). Six of 24 patients (25%) with FET avidity before radiation therapy showed focal gadolinium enhancement within the radiation therapy portal. ConclusionsFET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component. This may result in improved radiation therapy target delineation and reduce the risk of potential geographical miss. SummaryWe investigated the impact of 18F-fluoroethyltyrosine (FET) positron emission tomography (PET) on radiation therapy planning for patients diagnosed with glioblastoma (GBM) and a suspected nonenhancing tumor compared with standard magnetic resonance imaging. We performed volumetric analyses between clinical target volumes and respective biological target volumes using Wilcoxon signed-rank tests. FET-PET may help improve delineation of GBM in cases with a suspected nonenhancing component and reduce the risk of potential geographical miss.

In This Issue: November

In This Issue: November

Characterization of Gadolinium Contrast Enhancement of Radiofrequency Ablation Lesions in Predicting Edema and Chronic Lesion Size.

Magnetic resonance imaging (MRI) has been used to acutely visualize radiofrequency ablation lesions, but its accuracy in predicting chronic lesion size is unknown. The main goal of this study was to characterize different areas of enhancement in late gadolinium enhancement MRI done immediately after ablation to predict acute edema and chronic lesion size. In a canine model (n=10), ventricular radiofrequency lesions were created using ThermoCool SmartTouch (Biosense Webster) catheter. All animals underwent MRI (late gadolinium enhancement and T2-weighted edema imaging) immediately after ablation and after 1, 2, 4, and 8 weeks. Edema, microvascular obstruction, and enhanced volumes were identified in MRI and normalized to chronic histological volume. Immediately after contrast administration, the microvascular obstruction region was 3.2±1.1 times larger than the chronic lesion volume in acute MRI. Even 60 minutes after contrast administration, edema was 8.7±3.31 times and the enhanced area 6.14±2.74 times the chronic lesion volume. Exponential fit to the microvascular obstruction volume was found to be the best predictor of chronic lesion volume at 26.14 minutes (95% prediction interval, 24.35-28.11 minutes) after contrast injection. The edema volume in late gadolinium enhancement correlated well with edema volume in T2-weighted MRI with an R2 of 0.99. Microvascular obstruction region on acute late gadolinium enhancement images acquired 26.1 minutes after contrast administration can accurately predict the chronic lesion volume. We also show that T1-weighted MRI images acquired immediately after contrast injection accurately shows edema resulting from radiofrequency ablation.

The Use of T1W BB Signal Intensity Difference Ratio In Assessing Myocardial Disease Involving Increasing Extracellular Volume: A Preliminary Study

OBJECTIVE: To evaluate whether the new magnetic resonance imaging (MRI)technique related to T1 weighted black blood (T1W BB) signal intensity differenceratio between pre- and post- gadolinium contrast injection can serve as a potentialtechnique for use in differentiating normal and diseased myocardium involving theincreasing myocardial extracellular volume (ECV) in terms of sensitivity, specificityand accuracy in comparison with late gadolinium contrast enhancement (LGE) MRItechnique.MATERIALS AND METHODS: A retrospective analysis was conducted for a pilotof a total of 14 patients with known and suspected myocardial disease who underwenta cardiovascular magnetic resonance (CMR) scan at Bangkok Heart Hospital, Bangkok,Thailand in the period from September 2016-April 2017. LGE MRI and Spin echo T1WBB MRI in both pre- and post- contrast injection were performed in all patents on shortaxis view in the same slice position and number of slices. The myocardial signal intensitymeasurement on the T1W BB in both pre- and post- contrast injection images wereacquired on short axis view at the same region of interest (contrast enhancement regionand negative enhancement) on LGE MRI images. T1 signal intensity difference ratio(SDR) between pre- and post- contrast were calculated in both LGE positive andnegative groups. The mean T1W BB signal intensity difference ratio value &gt; 30% wasclassified as abnormal increased ECV myocardium.RESULTS: The 14 study population have a mean age of 53.3±11.5 and are 64% male.Five were normal patients with negative LGE and nine were found to have myocardialdisease with positive LGE. A total of 61 sample slices on short axis view of theventricle of each T1W BB pre- and post- contrast were obtained from all patients, 31of 61 were from diseased myocardium with LGE positive scan and 30 were from normalmyocardium with a LGE negative scan. A myocardial T1 signal difference ratio &gt; 30%was found in 2 of 30 slices of normal myocardium with the LGE negative group and 31of 31 slices of the LGE positive group. The mean signal difference ratio value of normaland diseased myocardium were 19.13±7.5 % and 41.4±7.6% respectively. The sensitivityand specificity and the accuracy of T1W BB difference ratio &gt; 30% in differentiatingnormal from myocardium with involving increasing ECV were 100%, 93.3% and 96.7%(p=0.72) consecutively compared to the LGE MRI.CONCLUSION: The use of T1W BB in assessing myocardial diseases with either afocal or diffuse involvement demonstrates a higher value ratio of extracellular spacepre- and post- contrast study of more than 30% indicating myocardial disease with 100%sensitivity and 93.3% in specificity and 96.7% accuracy that is shown to be comparableto gold standard LGE technique in detecting focal increasing myocardial ECV bystatistic chi-square test p =0.72 (not less than 0.05)

5-Aminolevulinic acid fluorescence guided resection of malignant glioma: Hong Kong experience

5-Aminolevulinic Acid (5-ALA) induced fluorescence is useful in guiding glioma resection. The extent of 5-ALA accumulation is beyond gadolinium contrast enhancement.1,2 Supratotal resection may be achieved, potentially granting patients with better survival. We present our experience on 5-ALA guided glioma resection in Chinese ethnics. Sixteen Patients ingested 5-ALA (Gliolan, Medas Germany) 20mg/kg·m2 4h before surgery. The tumor resection was guided by fluorescence with neurosurgical microscope. Patient was monitored for general condition, especially for new neurological deficits. Postoperative MRI served as the assessment for extent of resection (EOR). High grade glioma was confirmed in 12 cases, low grade glioma in three and one inflammation. 5-ALA was used in ten patients with known malignant glioma, and in six patients with presumed diagnosis of malignant glioma. Fifteen cases had positive fluorescence. The intensity was strong in eight and moderate in seven cases. MRI suggested total resection was achieved in 9 patients, near total resection in two and five had subtotal resection. EOR was associated with duration between ingestion of 5-ALA and timing when microscope was brought in for visualization of fluorescence (p=0.038). Two patients suffered from temporary visual field defects. One patient developed hemiparesis after surgery. 5-ALA is a useful intra-operative guidance for resection. It increases the percentageof total removal of the tumor. It should be used within the window period of the action (4-12h).

Cardiovascular magnetic resonance imaging to assess myocardial fibrosis in valvular heart disease

The left ventricular (LV) remodeling process associated with significant valvular heart disease (VHD) is characterized by an increase of myocardial interstitial space with deposition of collagen and loss of myofibers. These changes occur before LV systolic function deteriorates or the patient develops symptoms. Cardiovascular magnetic resonance (CMR) permits assessment of reactive fibrosis, with the use of T1 mapping techniques, and replacement fibrosis, with the use of late gadolinium contrast enhancement. In addition, functional consequences of these structural changes can be evaluated with myocardial tagging and feature tracking CMR, which assess the active deformation (strain) of the LV myocardium. Several studies have demonstrated that CMR techniques may be more sensitive than the conventional measures (LV ejection fraction or LV dimensions) to detect these structural and functional changes in patients with severe left-sided VHD and have shown that myocardial fibrosis may not be reversible after valve surgery. More important, the presence of myocardial fibrosis has been associated with lesser improvement in clinical symptoms and recovery of LV systolic function. Whether assessment of myocardial fibrosis may better select the patients with severe left-sided VHD who may benefit from surgery in terms of LV function and clinical symptoms improvement needs to be demonstrated in prospective studies. The present review article summarizes the current status of CMR techniques to assess myocardial fibrosis and appraises the current evidence on the use of these techniques for risk stratification of patients with severe aortic stenosis or regurgitation and mitral regurgitation.

Erratum to: Perfusion imaging of brain gliomas using arterial spin labeling: correlation with histopathological vascular density in MRI-guided biopsies.

This study was designed to determine if cerebral blood flow (CBF) derived from arterial spin labeling (ASL) perfusion imaging could be used to quantitatively evaluate the microvascular density (MVD) of brain gliomas on a “point-to-point” basis by matching CBF areas and surgical biopsy sites as accurate as possible. The study enrolled 47 patients with treatment-naive brain gliomas who underwent preoperative ASL, 3D T1-weighted imaging with gadolinium contrast enhancement (3D T1C+), and T2 fluid acquisition of inversion recovery (T2FLAIR) sequences before stereotactic surgery. We histologically quantified MVD from CD34-stained sections of stereotactic biopsies and co-registered biopsy locations with localized CBF measurements. The correlation between CBF and MVD was determined using Spearman’s correlation coefficient. P ≤ .05 was considered statistically significant. Of the 47 patients enrolled in the study, 6 were excluded from the analysis because of brain shift or poor co-registration and localization of the biopsy site during surgery. Finally, 84 biopsies from 41 subjects were included in the analysis. CBF showed a statistically significant positive correlation with MVD (ρ = 0.567; P = .029). ASL can be a useful noninvasive perfusion MR method for quantitative evaluation of the MVD of brain gliomas.

Gadolinium Contrast Enhancement Improves Confidence in Diagnosing Recurrent Soft Tissue Sarcoma by MRI

To determine how utilization of postgadolinium magnetic resonance imaging (MRI) influenced reader accuracy and confidence at identifying postoperative soft tissue sarcoma (STS) recurrence among readers with various levels of expertise. This retrospective study was institutional review board approved and Health Insurance Portability and Accountability Act compliant. Postoperative MRI from 26 patients with prior STS resection (13 patients with confirmed recurrence, 13 without recurrence) was reviewed. Four blinded readers of varying expertise (radiology resident, fellow, attending, and orthopedic oncologist) initially evaluated only the precontrast images and rated each MRI for recurrence on a 5-point confidence scale. Assessment was repeated with the addition of contrast-enhanced sequences. Diagnostic accuracy based on confidence ratings was evaluated using the area under the receiver operating characteristic curve (AUC). Changes in confidence ratings were calculated using Wilcoxon signed-rank test. All readers demonstrated good diagnostic accuracy both with and without contrast-enhanced images (AUC >0.98 for each reader). When contrast-enhanced images were made available, the resident recorded improved confidence with both assigning (P = 0.031) and excluding recurrence (P = 0.006); the fellow showed improved confidence only with assigning recurrence (P = 0.015); and the surgeon showed improved confidence in excluding recurrence (P = 0.003). The addition of contrast-enhanced images did not significantly influence the diagnostic confidence of the attending radiologist. Diagnostic accuracy of MRI was excellent in evaluating postoperative STS recurrence, and reader confidence improved depending on expertise when postgadolinium imaging was included in the assessment.

Perfusion imaging of brain gliomas using arterial spin labeling: correlation with histopathological vascular density in MRI-guided biopsies.

This study was designed to determine if cerebral blood flow (CBF) derived from arterial spin labeling (ASL) perfusion imaging could be used to quantitatively evaluate the microvascular density (MVD) of brain gliomas on a "point-to-point" basis by matching CBF areas and surgical biopsy sites as accurate as possible. The study enrolled 47 patients with treatment-naive brain gliomas who underwent preoperative ASL, 3D T1-weighted imaging with gadolinium contrast enhancement (3D T1C+), and T2 fluid acquisition of inversion recovery (T2FLAIR) sequences before stereotactic surgery. We histologically quantified MVD from CD34-stained sections of stereotactic biopsies and co-registered biopsy locations with localized CBF measurements. The correlation between CBF and MVD was determined using Spearman's correlation coefficient. P≤.05 was considered statistically significant. Of the 47 patients enrolled in the study, 6 were excluded from the analysis because of brain shift or poor co-registration and localization of the biopsy site during surgery. Finally, 84 biopsies from 41 subjects were included in the analysis. CBF showed a statistically significant positive correlation with MVD (ρ=0.567; P=.029). ASL can be a useful noninvasive perfusion MR method for quantitative evaluation of the MVD of brain gliomas.

Quantifying Intracranial Plaque Permeability with Dynamic Contrast-Enhanced MRI: A Pilot Study.

Intracranial atherosclerotic disease plaque hyperintensity and/or gadolinium contrast enhancement have been studied as imaging biomarkers of acutely symptomatic ischemic presentations using single static MR imaging measurements. However, the value in modeling the dynamics of intracranial plaque permeability has yet to be evaluated. The purpose of this study was to use dynamic contrast-enhanced MR imaging to quantify the contrast permeability of intracranial atherosclerotic disease plaques in symptomatic patients and to compare these parameters against existing markers of plaque volatility using black-blood MR imaging pulse sequences. We performed a prospective study of contrast uptake dynamics in the major intracranial vessels proximal and immediately distal to the circle of Willis using dynamic contrast-enhanced MR imaging, specifically in patients with symptomatic intracranial atherosclerotic disease. Using the Modified Tofts model, we extracted the volume transfer constant (Ktrans) and fractional plasma volume (Vp) parameters from plaque-enhancement curves. Using regression analyses, we compared these parameters against time from symptom onset as well as intraplaque hyperintensity and postcontrast enhancement derived from T1 SPACE, a black-blood MR vessel wall imaging sequence. We completed analysis in 10 patients presenting with symptomatic intracranial atherosclerotic disease. Ktrans and Vp measurements were higher in plaques versus healthy white matter and similar or less than values in the choroid plexus. Only Ktrans correlated significantly with time from symptom onset (P = .02). Dynamic contrast-enhanced MR imaging parameters were not found to correlate significantly with intraplaque enhancement or intraplaque hyperintensity (P = .4 and P = .17, respectively). Elevated Ktrans and Vp values found in intracranial atherosclerotic disease plaques versus healthy white matter suggest that dynamic contrast-enhanced MR imaging is a feasible technique for studying vessel wall and plaque characteristics in the proximal intracranial vasculature. Significant correlations between Ktrans and symptom onset, which were not observed on T1 SPACE-derived metrics, suggest that Ktrans may be an independent imaging biomarker of acute and symptom-associated pathologic changes in intracranial atherosclerotic disease plaques.

Magnetic Resonance Imaging-Based Radiomic Profiles Predict Patient Prognosis in Newly Diagnosed Glioblastoma Before Therapy

Magnetic resonance imaging (MRI) is used to diagnose and monitor brain tumors. Extracting additional information from medical imaging and relating it to a clinical variable of interest is broadly defined as radiomics. Here, multiparametric MRI radiomic profiles (RPs) of de novo glioblastoma (GBM) brain tumors is related with patient prognosis. Clinical imaging from 81 patients with GBM before surgery was analyzed. Four MRI contrasts were aligned, masked by margins defined by gadolinium contrast enhancement and T2/fluid attenuated inversion recovery hyperintensity, and contoured based on image intensity. These segmentations were combined for visualization and quantification by assigning a 4-digit numerical code to each voxel to indicate the segmented RP. Each RP volume was then compared with overall survival. A combined classifier was then generated on the basis of significant RPs and optimized volume thresholds. Five RPs were predictive of overall survival before therapy. Combining the RP classifiers into a single prognostic score predicted patient survival better than each alone (P < .005). Voxels coded with 1 RP associated with poor prognosis were pathologically confirmed to contain hypercellular tumor. This study applies radiomic profiling to de novo patients with GBM to determine imaging signatures associated with poor prognosis at tumor diagnosis. This tool may be useful for planning surgical resection or radiation treatment margins.

Etiological, clinical, and radiological features of longitudinally extensive myelopathy in Chinese patients

Longitudinally extensive myelopathy (LEM) is a rare spinal syndrome, and was mostly assessed in western populations. In order to investigate the etiological, clinical, and radiological features of LEM in Chinese patients, we retrospectively analyzed eighty-nine (40 men and 49 women, median age 45.9±15.7years) patients with LEM hospitalized in China-Japan Friendship Hospital. LEM comprised autoimmune inflammatory myelitis (n=53), metabolic and compressive disorders (n=13), vascular diseases (n=10), neoplastic diseases (n=7), infectious diseases (n=4), and syringomyelia (n=2). Neuromyelitis optica spectrum disorders (NMOSD) was the most common cause of transverse myelopathy identified in LEM (38/89 [42.7%]) characterized by intractable vomiting and hiccups and painful tonic spasms. Subacute combined degeneration and anterior spinal artery syndrome accounted for the largest non-transverse LEM, which selectively affected the spinal dorsal and/or lateral columns and the spinal anterior region, respectively. Radicular pain was common in anterior spinal artery syndrome. Postrema (n=15, 39.5%) and cervical (n=31, 81.6%) lesions were significantly increased in NMOSD versus non-NMOSD (n=7, 13.7% and n=34, 66.7%, respectively, p<0.05]. Axial T2-weighted MRI indicated that 46 (51.7%) patients exhibited complete lesions; 43 (48.3%) patients exhibited non-transverse lesions, mainly unilateral or symmetrical tract lesions. Twenty-four (51.1%) LEM patients exhibited distinct gadolinium contrast enhancement. In this Chinese cohort, LEM was primarily attributed to NMOSD. While the etiological distribution in the non-NMOSD group was different from western populations, clinical and imaging features may facilitate a differential diagnosis.