Perfusion MRI in the evaluation of brain metastases: current practice review and rationale for study of baseline MR perfusion imaging prior to stereotactic radiosurgery (STARBEAM-X).

Stereotactic radiosurgery is an established focal treatment for brain metastases with high local control rates. An important side-effect of stereotactic radiosurgery is the development of radionecrosis. On conventional MR imaging, radionecrosis and tumour progression often have similar appearances, but have contrasting management approaches. Perfusion MR imaging is often used in the post-treatment setting in order to help distinguish between the two, but image interpretation can be fraught with challenges.Perfusion MR plays an established role in the baseline and post-treatment evaluation of primary brain tumours and a number of studies have concentrated on the value of perfusion imaging in brain metastases. Of the parameters generated, relative cerebral blood volume is the most widely used variable in terms of its clinical value in differentiating between radionecrosis and tumour progression. Although it has been suggested that the relative cerebral blood volume tends to be elevated in active metastatic disease following treatment with radiosurgery, but not with treatment-related changes, the literature available on interpretation of the ratios provided in the context of defining tumour progression is not consistent.This article aims to provide an overview of the role perfusion MRI plays in the assessment of brain metastases and introduces the rationale for the STARBEAM-X study (Study of assessment of radionecrosis in brain metastases using MR perfusion extra imaging), which will prospectively evaluate baseline perfusion imaging in brain metastases. We hope this will allow insight into the vascular appearance of metastases from different primary sites, and aid in the interpretation of post-treatment perfusion imaging.

Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study.

BACKGROUND: In neonatal encephalopathy, the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance (MR) spectroscopy (MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after neonatal encephalopathy. METHODS: We did a prospective multicentre cohort study across eight neonatal intensive care units in the UK and USA, recruiting term and near-term neonates who received therapeutic hypothermia for neonatal encephalopathy. We excluded infants with life-threatening congenital malformations, syndromic disorders, neurometabolic diseases, or any alternative diagnoses for encephalopathy that were apparent within 6 h of birth. We obtained T1-weighted, T2-weighted, and diffusion-weighted MRI and thalamic proton MRS 4-14 days after birth. Clinical neurodevelopmental tests were done 18-24 months later. The primary outcome was the association between MR biomarkers and an adverse neurodevelopmental outcome, defined as death or moderate or severe disability, measured using a multivariable prognostic model. We used receiver operating characteristic (ROC) curves to examine the prognostic accuracy of the individual biomarkers. This trial is registered with ClinicalTrials.gov, number NCT01309711. FINDINGS: Between Jan 29, 2013, and June 25, 2016, we recruited 223 infants who all underwent MRI and MRS at a median age of 7 days (IQR 5-10), with 190 (85%) followed up for neurological examination at a median age of 23 months (20-25). Of those followed up, 31 (16%) had moderate or severe disability, including one death. Multiple logistic regression analysis could not be done because thalamic N-acetylaspartate (NAA) concentration alone accurately predicted an adverse neurodevelopmental outcome (area under the curve [AUC] of 0·99 [95% CI 0·94-1·00]; sensitivity 100% [74-100]; specificity 97% [90-100]; n=82); the models would not converge when any additional variable was examined. The AUC (95% CI) of clinical examination at 6 h (n=190) and at discharge (n=167) were 0·72 (0·65-0·78) and 0·60 (0·53-0·68), respectively, and the AUC of abnormal amplitude integrated EEG at 6 h (n=169) was 0·73 (0·65-0·79). On conventional MRI (n=190), cortical injury had an AUC of 0·67 (0·60-0·73), basal ganglia or thalamic injury had an AUC of 0·81 (0·75-0·87), and abnormal signal in the posterior limb of internal capsule (PLIC) had an AUC of 0·82 (0·76-0·87). Fractional anisotropy of PLIC (n=65) had an AUC of 0·82 (0·76-0·87). MRS metabolite peak-area ratios (n=160) of NAA-creatine (<1·29) had an AUC of 0·79 (0·72-0·85), of NAA-choline had an AUC of 0·74 (0·66-0·80), and of lactate-NAA (>0·22) had an AUC of 0·94 (0·89-0·97). INTERPRETATION: Thalamic proton MRS measures acquired soon after birth in neonatal encephalopathy had the highest accuracy to predict neurdevelopment 2 years later. These methods could be applied to increase the power of neuroprotection trials while reducing their duration. FUNDING: National Institute for Health Research UK.

Predictive value of flexion and extension diffusion tensor imaging in the early stage of cervical myelopathy.

PURPOSE: Diffusion tensor imaging (DTI) in flexion (F) and extension (E) may serve as a sensitive diagnostic tool in early symptoms of myelopathy. The aim of this study was to compare values of water diffusion parameters on dynamic cervical DTI in early stage of myelopathy. METHODS: Study enrolled 10 patients with an early stage of cervical myelopathy, in grade I/II of Nurick classification. All subjects were scanned with flexion-extension 3T MRI. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), RD (radial diffusivity), AD (axial diffusivity) and TRACEW (trace diffusion) were measured at C2, compression level (CL) and C7. Parameters were compared between 3 levels and F and E positions. RESULTS: Flexion DTI revealed significant difference only for TRACEW between C2 and C7 (105.8 ± 18.9 vs. 83.7 ± 14, respectively; p = 0.0029). Extension DTI showed differences for ADC between CL and C7 (1378.9 ± 381.8 vs. 1227.2 ± 269.2; p = 0.001), reduced FA from 664.6 ± 56.3 at C2 down to 553.1 ± 75.5 (p = 0.001) at CL and 584.7 ± 40.7 at C7 (p = 0.002). Differences of RD in E were significant through all levels and reached 612.9 ± 105.1, 955.3 ± 319.4 and 802.1 ± 194.1 at C2, CL and C7, respectively. TRACEW lowered from 92.3 ± 14.4 at C2 to 66.9 ± 21.1 at CL (p = 0.0001) and 64.4 ± 15.5 at C7 (p = 0.0002). Comparison of DTI between F and E showed differences for all parameters except AD. RD was significantly higher in E at CL (p = 0.003) and C7 (0.013), but TRACEW increased in F at CL by 27.4% (p = 0.001) and at C7 by 23.1% (p = 0.013). FA was reduced at CL in E (p = 0.027) and similarly ADC in F (p = 0.048). CONCLUSION: Dynamic DTI of the cervical spine is feasible and can detect subtle spinal cord damage of functional relevance in cervical myelopathy. A marked increase of RD and decrease of FA and TRACEW values in extension were found to be indicative for an early structural cord injury in myelopathy.

Distinct critical cerebellar subregions for components of verbal working memory.

A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between cognitive performance and cerebellar integrity in a specific degeneration of the cerebellar cortex: Spinocerebellar Ataxia type 6 (SCA6). The results demonstrate a critical relationship between verbal working memory and grey matter density in superior (bilateral lobules VI and crus I of lobule VII) and inferior (bilateral lobules VIIIa and VIIIb, and right lobule IX) parts of the cerebellum. We demonstrate that distinct cerebellar regions subserve different components of the prevalent psychological model for verbal working memory based on a phonological loop. The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum.

Preoperative MRI/MRA for microvascular decompression in trigeminal neuralgia: consecutive series of 67 patients.

BACKGROUND: Microvascular decompression is an accepted treatment for primary trigeminal neuralgia. In recent years, efforts have been made to investigate the role of preoperative MRI/MRA in selecting patients with neurovascular compression. METHODS: Ninety-two consecutive patients underwent a standard retrosigmoid craniotomy for microvascular decompression between 2005 and 2009, of whom 67 had a preoperative MRI and MRA according to the protocol of our department. Operative findings were accurately recorded and compared to MRI/MRA results. Follow-up was in the form of telephone interview. RESULTS: Preoperative MRI sensitivity was 96%, while specificity was 75% (1 false positive among 4 patients with negative intra-operative findings). The predictive value of a positive MRI/MRA was 98%, while the predictive value of a negative MRI/MRA was 50%. Fifty-four patients were available for outcome assessment at a mean follow-up of 3.8 years (range 1-5). Seventy-two percent of patients were pain-free, 9.5% had mild residual pain, while 18.5% had a poor outcome (moderate to severe residual pain). The correlation between preoperative MRI/MRA and outcome was not statistically significant (P = 0.570). CONCLUSIONS: Preoperative MRI has both good sensitivity and positive predictive value. Specificity and negative predicitve value were limited in this series. No correlation was found between preoperative imaging and outcome. Both radiological and clinical criteria are important for patient selection.

Intra-operative MRI-assisted spinal localization.

BACKGROUND: Level localization in the thoracic spine can be problematic. We describe a new method that can be used in difficult cases, e.g., ones where lesions are mid-thoracic, small, or only visible on MRI. METHODS: Intra-operatively, a midline incision was made and the thoracic spinous processes were exposed. A length of contrast-filled tubing was wound around the processes and the incision was temporarily closed and the patient was transferred to the radiology department for MRI under general anesthetic. Upon return to theatre, the cross sections of contrast-filled tubing and the lesion itself were visible on the MRI scan, allowing localization of the level. FINDINGS: This method was accurate and minimized the extent of bone removal required for access. CONCLUSIONS: This technique, while not appropriate in every case, is repeatable, and does not require specialized equipment or training. It is an extremely accurate method of localization for difficult cases.

Pioglitazone decreases fasting and postprandial endogenous glucose production in proportion to decrease in hepatic triglyceride content.

OBJECTIVE: Hepatic triglyceride is closely associated with hepatic insulin resistance and is known to be decreased by thiazolididinediones. We studied the effect of pioglitazone on hepatic triglyceride content and the consequent effect on postprandial endogenous glucose production (EGP) in type 2 diabetes. RESEARCH DESIGN AND METHODS: Ten subjects with type 2 diabetes on sulfonylurea therapy were treated with pioglitazone (30 mg daily) for 16 weeks. EGP was measured using a dynamic isotopic methodology after a standard liquid test meal both before and after pioglitazone treatment. Liver and muscle triglyceride levels were measured by (1)H magnetic resonance spectroscopy, and intra-abdominal fat content was measured by magnetic resonance imaging. RESULTS: Pioglitazone treatment reduced mean plasma fasting glucose and mean peak postprandial glucose levels. Fasting EGP decreased after pioglitazone treatment (16.6 +/- 1.0 vs. 12.2 +/- 0.7 micromol . kg(-1) . min(-1), P = 0.005). Between 80 and 260 min postprandially, EGP was twofold lower on pioglitazone (2.58 +/- 0.25 vs. 1.26 +/- 0.30 micromol . kg(-1) . min(-1), P < 0.001). Hepatic triglyceride content decreased by approximately 50% (P = 0.03), and muscle (anterior tibialis) triglyceride content decreased by approximately 55% (P = 0.02). Hepatic triglyceride content was directly correlated with fasting EGP (r = 0.64, P = 0.01) and inversely correlated to percentage suppression of EGP (time 150 min, r = -0.63, P = 0.02). Muscle triglyceride, subcutaneous fat, and visceral fat content were not related to EGP. CONCLUSIONS Reduction in hepatic triglyceride by pioglitazone is very closely related to improvement in fasting and postprandial EGP in type 2 diabetes.

Diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease.

Dementia with Lewy bodies (DLB) is a common form of dementia, with fewer memory deficits, and more visuo-perceptual problems than Alzheimer's disease (AD). We hypothesized that there would be disease specific alterations revealed by diffusion tensor imaging with AD showing temporal lobe and DLB more parietal changes. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with diffusion tensor FLAIR imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were calculated, and data were analysed using pre-defined regions of interest (ROI) and also with SPM. We found a significant decrease in the FA map in a ROI in the parietal lobe (precuneus) of the DLB group. Using SPM we found increased ADC in the left temporal lobe of AD subjects compared to controls. There were no other significant differences between groups. We conclude that there are subtle changes visible with diffusion imaging in DLB and AD which may reflect disrupted connectivity and underlie observed perfusion changes in these disorders.

Atrophy is associated with posterior cingulate white matter disruption in dementia with Lewy bodies and Alzheimer's disease.

Hippocampal atrophy and posterior cingulate hypometabolism are common features of both Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). These regions show correlated activity at rest as part of the 'default network', and they are connected by the cingulum, a white matter (WM) tract. We hypothesised that hippocampal atrophy would be associated with disruption of the cingulum, as determined by diffusion tensor imaging. We recruited 15 people with AD, 16 with DLB, and 15 healthy control subjects of similar age. They were scanned on a 1.5 T MRI system with a T1 weighted 3D sequence and diffusion tensor FLAIR imaging. The T1 images were segmented into grey and white matter and spatially normalised using SPM. Hippocampal atrophy was estimated by calculating the mean grey matter (GM) volume from a region of interest in standard space and global atrophy from the total CSF segmentation. Fractional anisotropy (FA) maps were calculated and also spatially normalised. Using SPM, a multivariate correlation of FA against hippocampal GM, global atrophy and disease group was performed. We found a bilateral region adjacent to the posterior cingulate and encompassing a branch of the cingulum where global atrophy correlated with fractional anisotropy, after controlling for diagnosis and hippocampal GM. The results suggest that dementia disease progression as measured by global atrophy is associated with disruption of the white matter which connects posterior cingulate and lateral parietal regions. Hence, in addition to the hypometabolism in these regions in AD and DLB, there is also disruption to the white matter connecting them. Future studies are needed to determine whether the disruption precedes or is consequent on atrophy or hypometabolism.

Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients.

OBJECTIVES: Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly subjects, but their clinical significance is controversial. The authors sought to determine whether SMCs are related to WML, independently of the presence of depressive symptoms, which are known to be associated with both. The relationship between SMC and cognition was also examined. METHODS: This is a cross-sectional study on 60 elderly subjects without dementia. All subjects underwent FLAIR and T2-weighted axial MRI scans, a memory-complaint questionnaire, a geriatric depression scale, and a comprehensive cognitive assessment. RESULTS: Multiple linear regression showed that although the best correlate of SMC was the severity of depressive symptoms, SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. CONCLUSIONS: Complaints of cognitive decline are significantly associated with the severity of WML, independently of level of cognition and depression.

Acute inhibition of lipolysis does not affect postprandial suppression of endogenous glucose production.

To test the hypothesis that intrahepatic availability of fatty acid could modify the rate of suppression of endogenous glucose production (EGP), acipimox or placebo was administered before and during a test meal. We used a modified isotopic methodology to measure EGP in 11 healthy subjects, and (1)H magnetic resonance spectroscopic measurement of hepatic triglyceride stores was also undertaken. Acipimox suppressed plasma free fatty acids markedly before the meal (0.05 +/- 0.01 mmol/l at -10 min, P = 0) and throughout the postprandial period (0.03 +/- 0.01 mmol/l at 150 min). Mean peak plasma glucose was significantly lower after the meal on acipimox days (8.9 +/- 0.4 vs. 10.1 +/- 0.5 mmol/l, P < 0.01), as was mean peak serum insulin (653.1 +/- 99.9 vs. 909 +/- 118 pmol/l, P < 0.01). Fasting EGP was similar (11.15 +/- 0.58 micromol.kg(-1).min(-1) placebo vs. 11.17 +/- 0.89 mg.kg(-1).min(-1) acipimox). The rate of suppression of EGP after the meal was almost identical on the 2 test days (4.36 +/- 1.52 vs. 3.69 +/- 1.21 micromol.kg(-1).min(-1) at 40 min). There was a significant negative correlation between the acipimox-induced decrease in peak plasma glucose and liver triglyceride content (r = -0.827, P = 0.002), suggesting that, when levels of liver fat were low, inhibition of lipolysis was able to affect glucose homeostasis. Acute pharmacological sequestration of fatty acids in triglyceride stores improves postprandial glucose homeostasis without effect on the immediate postprandial suppression of EGP.