Perioperative research into memory (PRiMe), part 2: Adult burns intensive care patients show altered structure and function of the default mode network.

BACKGROUND: Long-term cognitive impairment (LTCI) is experienced by up to two thirds of patients discharged from burns intensive care units (BICUs), however little is known about its neurobiological basis. This study investigated if patients previously admitted to BICU showed structural and functional MRI changes of the Default Mode Network (DMN). METHODS: Fifteen patients previously admitted to BICU with a significant burns injury, and 15 matched volunteers, underwent structural and functional MRI scans. Functional connectivity, fractional anisotropy and cortical thickness of the main DMN subdivisions (anterior DMN (aDMN), posterior DMN (pDMN) and right (rTPJ) and left (lTPJ) temporo-parietal junctions) were compared between patients and volunteers, with differences correlated against cognitive performance. RESULTS: Functional connectivity between rTPJ and pDMN (t = 2.91, p = 0.011) and between rTPJ and lTPJ (t = 3.18, p = 0.008) was lower in patients compared to volunteers. Functional connectivity between rTPJ and pDMN correlated with cognitive performance (r2 =0.33, p < 0.001). Mean fractional anisotropy of rTPJ (t = 2.70, p = 0.008) and lTPJ (T = 2.39, p = 0.015) was lower in patients but there was no difference in cortical thickness. CONCLUSIONS: Patients previously admitted to BICU show structural and functional disruption of the DMN. Since functional changes correlate with cognitive performance, this should direct further research into intensive-care-related cognitive impairment.

Temperature dependence, accuracy, and repeatability of T1 and T2 relaxation times for the ISMRM/NIST system phantom measured using MR fingerprinting.

PURPOSE: Before MR fingerprinting (MRF) can be adopted clinically, the derived quantitative values must be proven accurate and repeatable over a range of T1 and T2 values and temperatures. Correct assessment of accuracy and precision as well as comparison between measurements can only be performed when temperature is either controlled or corrected for. The purpose of this study was to investigate the temperature dependence of T1 and T2 MRF values and evaluate the accuracy and repeatability of temperature-corrected relaxation values derived from a B1 -corrected MRF-fast imaging with steady-state precession implementation using 2 different dictionary sizes. METHODS: The International Society of MR in Medicine/National Institute of Standards and Technology phantom was scanned using an MRF sequence of 2 different lengths, a variable flip angle T1 , and a multi-echo spin echo T2 at 14 temperatures ranging from 15°C to 28°C and investigated with a linear regression model. Temperature-corrected accuracy was evaluated by correlating T1 and T2 times from each MRF dictionary with reference values. Repeatability was assessed using the coefficient of variation, with measurements taken over 30 separate sessions. RESULTS: There was a statistically significant fit of the model for MRF-derived T1 and T2 and temperature (p < 0.05) for all the spheres with a T1 > 500 ms. Both MRF methods showed a strong linear correlation with reference values for T1 (R2 = 0.996) and T2 (R2 = 0.982). MRF repeatability for T1 values was ≤1.4% and for T2 values was ≤3.4%. CONCLUSION: MRF demonstrated relaxation times with a temperature dependence similar to that of conventional mapping methods. Temperature-corrected T1 and T2 values from both dictionaries showed adequate accuracy and excellent repeatability in this phantom study.

Understanding lower limb muscle volume adaptations to amputation.

Amputation of a major limb, and the subsequent return to movement with a prosthesis, requires the development of compensatory strategies to account for the loss. Such strategies, over time, lead to regional muscle atrophy and hypertrophy through chronic under or overuse of muscles compared to uninjured individuals. The aim of this study was to quantify the lower limb muscle parameters of persons with transtibial and transfemoral amputations using high resolution MRI to ascertain muscle volume and to determine regression equations for predicting muscle volume using femur- and tibia-length, pelvic-width, height, and mass. Twelve persons with limb loss participated in this study and their data were compared to six matched control subjects. Subjects with unilateral transtibial amputation showed whole-limb muscle volume loss in the residual-limb, whereas minor volume changes in the intact limb were found, providing evidence for a compensation strategy that is dominated by the intact-limb. Subjects with bilateral-transfemoral amputations showed significant muscle volume increases in the short adductor muscles with an insertion not affected by the amputation, the hip flexors, and the gluteus medius, and significant volume decreases in the longer adductor muscles, rectus femoris, and hamstrings. This study presents a benchmark measure of muscle volume discrepancies in persons with limb-loss, and can be used to understand the compensation strategies of persons with limb-loss and the impact on muscle volume, thus enabling the development of optimised intervention protocols, conditioning therapies, surgical techniques, and prosthetic devices that promote and enhance functional capability within the population of persons with limb loss.

Diffusion-weighted MRI in Advanced Epithelial Ovarian Cancer: Apparent Diffusion Coefficient as a Response Marker.

Background Treatment of advanced epithelial ovarian cancer results in a relapse rate of 75%. Early markers of response would enable optimization of management and improved outcome in both primary and recurrent disease. Purpose To assess the apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI, as an indicator of response, progression-free survival (PFS), and overall survival. Materials and Methods This prospective multicenter trial (from 2012-2016) recruited participants with stage III or IV ovarian, primary peritoneal, or fallopian tube cancer (newly diagnosed, cohort one; relapsed, cohort two) scheduled for platinum-based chemotherapy, with interval debulking surgery in cohort one. Cohort one underwent two baseline MRI examinations separated by 0-7 days to assess ADC repeatability; an additional MRI was performed after three treatment cycles. Cohort two underwent imaging at baseline and after one and three treatment cycles. ADC changes in responders and nonresponders were compared (Wilcoxon rank sum tests). PFS and overall survival were assessed by using a multivariable Cox model. Results A total of 125 participants (median age, 63.3 years [interquartile range, 57.0-70.7 years]; 125 women; cohort one, n = 47; cohort two, n = 78) were included. Baseline ADC (range, 77-258 × 10-5mm2s-1) was repeatable (upper and lower 95% limits of agreement of 12 × 10-5mm2s-1 [95% confidence interval {CI}: 6 × 10-5mm2s-1 to 18 × 10-5mm2s-1] and -15 × 10-5mm2s-1 [95% CI: -21 × 10-5mm2s-1 to -9 × 10-5mm2s-1]). ADC increased in 47% of cohort two after one treatment cycle, and in 58% and 53% of cohorts one and two, respectively, after three cycles. Percentage change from baseline differed between responders and nonresponders after three cycles (16.6% vs 3.9%; P = .02 [biochemical response definition]; 19.0% vs 6.2%; P = .04 [radiologic definition]). ADC increase after one cycle was associated with longer PFS in cohort two (adjusted hazard ratio, 0.86; 95% CI: 0.75, 0.98; P = .03). ADC change was not indicative of overall survival for either cohort. Conclusion After three cycles of platinum-based chemotherapy, apparent diffusion coefficient (ADC) changes are indicative of response. After one treatment cycle, increased ADC is indicative of improved progression-free survival in relapsed disease. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Anthropometric Scaling of Anatomical Datasets for Subject-Specific Musculoskeletal Modelling of the Shoulder.

Linear scaling of generic shoulder models leads to substantial errors in model predictions. Customisation of shoulder modelling through magnetic resonance imaging (MRI) improves modelling outcomes, but model development is time and technology intensive. This study aims to validate 10 MRI-based shoulder models, identify the best combinations of anthropometric parameters for model scaling, and quantify the improvement in model predictions of glenohumeral loading through anthropometric scaling from this anatomical atlas. The shoulder anatomy was modelled using a validated musculoskeletal model (UKNSM). Ten subject-specific models were developed through manual digitisation of model parameters from high-resolution MRI. Kinematic data of 16 functional daily activities were collected using a 10-camera optical motion capture system. Subject-specific model predictions were validated with measured muscle activations. The MRI-based shoulder models show good agreement with measured muscle activations. A tenfold cross-validation using the validated personalised shoulder models demonstrates that linear scaling of anthropometric datasets with the most similar ratio of body height to shoulder width and from the same gender (p < 0.04) yields best modelling outcomes in glenohumeral loading. The improvement in model reliability is significant (p < 0.02) when compared to the linearly scaled-generic UKNSM. This study may facilitate the clinical application of musculoskeletal shoulder modelling to aid surgical decision-making.

Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions.

Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between "younger" and "older" onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses. 21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls (n = 31, 31.9 ± 3.5 years and n = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors. Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group (p < 0.001) and a strong trend in the older-onset group. These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.

Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia.

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

A framework for optimization of diffusion-weighted MRI protocols for large field-of-view abdominal-pelvic imaging in multicenter studies.

PURPOSE: To develop methods for optimization of diffusion-weighted MRI (DW-MRI) in the abdomen and pelvis on 1.5 T MR scanners from three manufacturers and assess repeatability of apparent diffusion coefficient (ADC) estimates in a temperature-controlled phantom and abdominal and pelvic organs in healthy volunteers. METHODS: Geometric distortion, ghosting, fat suppression, and repeatability and homogeneity of ADC estimates were assessed using phantoms and volunteers. Healthy volunteers (ten per scanner) were each scanned twice on the same scanner. One volunteer traveled to all three institutions in order to provide images for qualitative comparison. The common volunteer was excluded from quantitative analysis of the data from scanners 2 and 3 in order to ensure statistical independence, giving n = 10 on scanner 1 and n = 9 on scanners 2 and 3 for quantitative analysis. Repeatability and interscanner variation of ADC estimates in kidneys, liver, spleen, and uterus were assessed using within-patient coefficient of variation (wCV) and Kruskal-Wallis tests, respectively. RESULTS: The coefficient of variation of ADC estimates in the temperature-controlled phantom was 1%-4% for all scanners. Images of healthy volunteers from all scanners showed homogeneous fat suppression and no marked ghosting or geometric distortion. The wCV of ADC estimates was 2%-4% for kidneys, 3%-7% for liver, 6%-9% for spleen, and 7%-10% for uterus. ADC estimates in kidneys, spleen, and uterus showed no significant difference between scanners but a significant difference was observed in liver (p < 0.05). CONCLUSIONS: DW-MRI protocols can be optimized using simple phantom measurements to produce good quality images in the abdomen and pelvis at 1.5 T with repeatable quantitative measurements in a multicenter study.

Biasing visual selection: functional neuroimaging of the interplay between spatial cueing and feature memory guidance.

The authors investigate the interplay between spatial attention and memory-based feature guidance of visual selection. Three types of guidance were tested: working memory, spatial cueing and passive memory. In all cases the memory-cue was not relevant to a subsequent search task, whilst the spatial cue always provided valid information. Behaviourally, search performance was influenced by spatial cueing and by feature-based cueing from the contents of working memory; both forms of guidance interacted, with feature guidance being more effective when the target's location was not pre-cued. Spatial cueing recruited the dorsal fronto-parietal network which was silent during the WM-only condition. Memory guidance of selection was reflected in activity in a frontal-temporal-occipital network. Interestingly, when spatial and memory guidance were pitted against each other, neural activity in this latter network was greatly attenuated. Connectivity analysis showed that the posterior parietal cortices inhibit the responses of occipital and temporal regions to the onset of memory-items in the search display. In the presence of a reliable spatial cue the posterior parietal cortex resumes control of attentional deployment. These results illustrate how different forms of attention guidance interact to optimise visual selection.

Flow measurement by cardiovascular magnetic resonance: a multi-centre multi-vendor study of background phase offset errors that can compromise the accuracy of derived regurgitant or shunt flow measurements.

AIMS: Cardiovascular magnetic resonance (CMR) allows non-invasive phase contrast measurements of flow through planes transecting large vessels. However, some clinically valuable applications are highly sensitive to errors caused by small offsets of measured velocities if these are not adequately corrected, for example by the use of static tissue or static phantom correction of the offset error. We studied the severity of uncorrected velocity offset errors across sites and CMR systems. METHODS AND RESULTS: In a multi-centre, multi-vendor study, breath-hold through-plane retrospectively ECG-gated phase contrast acquisitions, as are used clinically for aortic and pulmonary flow measurement, were applied to static gelatin phantoms in twelve 1.5 T CMR systems, using a velocity encoding range of 150 cm/s. No post-processing corrections of offsets were implemented. The greatest uncorrected velocity offset, taken as an average over a 'great vessel' region (30 mm diameter) located up to 70 mm in-plane distance from the magnet isocenter, ranged from 0.4 cm/s to 4.9 cm/s. It averaged 2.7 cm/s over all the planes and systems. By theoretical calculation, a velocity offset error of 0.6 cm/s (representing just 0.4% of a 150 cm/s velocity encoding range) is barely acceptable, potentially causing about 5% miscalculation of cardiac output and up to 10% error in shunt measurement. CONCLUSION: In the absence of hardware or software upgrades able to reduce phase offset errors, all the systems tested appeared to require post-acquisition correction to achieve consistently reliable breath-hold measurements of flow. The effectiveness of offset correction software will still need testing with respect to clinical flow acquisitions.

Changes in brain morphology associated with obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) causes hypoxemia and fragmented sleep, which lead to neurocognitive deficits. We hypothesised that focal loss of cortical gray matter generally within areas associated with memory processing and learning and specifically within the hippocampus would occur in OSA. METHODS: Voxel-based morphometry, an automated processing technique for magnetic resonance images, was used to characterise structural changes in gray matter in seven right handed, male patients with newly diagnosed OSA and seven non-apneic, male controls matched for handedness and age. RESULTS: The analysis revealed a significantly lower gray matter concentration within the left hippocampus (p=0.004) in the apneic patients. No further significant focal gray matter differences were seen in the right hippocampus and in other brain regions. There was no difference in total gray matter volume between apneics and controls. CONCLUSION: This preliminary report indicates changes in brain morphology in OSA, in the hippocampus, a key area for cognitive processing.

Differential cortical activation during voluntary and reflexive saccades in man.

A saccade involves both a step in eye position and an obligatory shift in spatial attention. The traditional division of saccades into two types, the "reflexive" saccade made in response to an exogenous stimulus change in the visual periphery and the "voluntary" saccade based on an endogenous judgement to move gaze, is supported by lines of evidence which include the longer onset latency of the latter and the differential effects of lesions in humans and primates on each. It has been supposed that differences between the two types of saccade derive from differences in how the spatial attention shifts involved in each are processed. However, while functional imaging studies have affirmed the close link between saccades and attentional shifts by showing they activate overlapping cortical networks, attempts to contrast exogenous with endogenous ("covert") attentional shifts directly have not revealed separate patterns of cortical activation. We took the "overt" approach, contrasting whole reflexive and voluntary saccades using event-related fMRI. This demonstrated that, relative to reflexive saccades, voluntary saccades produced greater activation within the frontal eye fields and the saccade-related area of the intraparietal sulci. The reverse contrast showed reflexive saccades to be associated with relative activation of the angular gyrus of the inferior parietal lobule, strongest in the right hemisphere. The frequent involvement of the right inferior parietal lobule in lesions causing hemispatial neglect has long implicated this parietal region in an important, though as yet uncertain, role in the awareness and exploration of space. This is the first study to demonstrate preferential activation of an area in its posterior part, the right angular gyrus, during production of exogenously triggered rather than endogenously generated saccades, a finding which we propose is consistent with an important role for the angular gyrus in exogenous saccadic orienting.

Studies of the human oropharyngeal airspaces using magnetic resonance imaging. I. Validation of a three-dimensional MRI method for producing ex vivo virtual and physical casts of the oropharyngeal airways during inspiration.

The oropharyngeal region of the human airways has been scanned using 3D MRI and the data used to produce a model cast. The scanning method used a triggering device, which enabled data collection at the same pressure drop in each breathing cycle to produce clear images free of motion-related artefacts. A comparison between two differing MR acquisition strategies was made in a single subject, multi-session study. 3D FISP MR imaging was found to produce the most reliable data. Excluding the buccal cavity, where tongue position was critical, the reproducibility of measured airway volumes and cross sectional areas between sessions was demonstrated. Inter-session total airway volume (excluding the mouth) reproducibility was of the order of 5% and for minimum cross sectional areas at the epiglottis and vocal cords was 10%. The production of a physical cast from the images led to a 5% increase in airway volume compared with the anatomical images but with some loss of fine detail. The data demonstrated the robustness of an ex-vivo means of studying oropharyngeal dimensions and dynamics which may contribute to advancements in the understanding of aerosol delivery of therapeutic agents.