Claire Bernard

METABOLIC ACTIVITY IN EXTERNAL AND INTERNAL AWARENESS NETWORKS IN SEVERELY BRAIN-DAMAGED PATIENTS

OBJECTIVE An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. DESIGN Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. SUBJECTS Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). RESULTS A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. CONCLUSION Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside.

Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients

The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.

Quantitative capabilities of four state-of-the-art SPECT-CT cameras

BackgroundFour state-of-the-art single-photon emission computed tomography-computed tomography (SPECT-CT) systems, namely Philips Brightview, General Electric Discovery NM/CT 670 and Infinia Hawkeye 4, and Siemens Symbia T6, were investigated in terms of accuracy of attenuation and scatter correction, contrast recovery for small hot and cold structures, and quantitative capabilities when using their dedicated three-dimensional iterative reconstruction with attenuation and scatter corrections and resolution recovery.MethodsThe National Electrical Manufacturers Association (NEMA) NU-2 1994 phantom with cold air, water, and Teflon inserts, and a homemade contrast phantom with hot and cold rods were filled with 99mTc and scanned. The acquisition parameters were chosen to provide adequate linear and angular sampling and high count statistics. The data were reconstructed using Philips Astonish, General Electric Evolution for Bone, or Siemens Flash3D, eight subsets, and a varying number of iterations. A procedure similar to the one used in positron emission tomography (PET) allowed us to obtain the factor to convert counts per pixel into activity per unit volume.ResultsEdge and oscillation artifacts were observed with all phantoms and all systems. At 30 iterations, the residual fraction in the inserts of the NEMA phantom fell below 3.5%. Contrast recovery increased with the number of iterations but became almost saturated at 24 iterations onwards. In the uniform part of the NEMA and contrast phantoms, a quantification error below 10% was achieved.ConclusionsIn objects whose dimensions exceeded the SPECT spatial resolution by several times, quantification seemed to be feasible within 10% error limits. A partial volume effect correction strategy remains necessary for the smallest structures. The reconstruction artifacts nevertheless remain a handicap on the road towards accurate quantification in SPECT and should be the focus of further works in reconstruction tomography.

Changes in cerebral metabolism in patients with a minimally conscious state responding to zolpidem

Background: Zolpidem, a short-acting non-benzodiazepine GABA agonist hypnotic, has been shown to induce paradoxical responses in some patients with disorders of consciousness (DOC), leading to recovery of arousal and cognitive abilities. We here assessed zolpidem-induced changes in regional brain metabolism in three patients with known zolpidem response in chronic post-anoxic minimally conscious state (MCS). Methods: [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and standardized clinical assessments using the Coma Recovery Scale-Revised were performed after administration of 10 mg zolpidem or placebo in a randomized double blind 2-day protocol. PET data preprocessing and comparison with a healthy age-matched control group were performed using statistical parametric mapping (SPM8). Results: Behaviorally, all patients recovered functional communication after administration of zolpidem (i.e., emergence from the MCS). FDG-PET showed increased metabolism in dorsolateral prefrontal and mesiofrontal cortices after zolpidem but not after placebo administration. Conclusion: Our data show a metabolic activation of prefrontal areas, corroborating the proposed mesocircuit hypothesis to explain the paradoxical effect of zolpidem observed in some patients with DOC. It also suggests the key role of the prefrontal cortices in the recovery of functional communication and object use in hypoxic patients with chronic MCS.

Nociception Coma Scale-Revised Scores Correlate With Metabolism in the Anterior Cingulate Cortex

Background. The Nociception Coma Scale–Revised (NCS-R) was recently validated to assess possible pain perception in patients with disorders of consciousness. Objective. To identify correlations between cerebral glucose metabolism and NCS-R total scores. Methods. [18F]-fluorodeoxyglucose positron emission tomography, NCS-R, and Coma Recovery Scale–Revised assessments were performed in 49 patients with disorders of consciousness. Results. We identified a significant positive correlation between NCS-R total scores and metabolism in the posterior part of the anterior cingulate cortex, known to be involved in pain processing. No other cluster reached significance. No significant effect of clinical diagnosis (vegetative/unresponsive vs minimally conscious states), etiology or interval since insult was observed. Conclusions. Our data support the hypothesis that the NCS-R total scores are related to cortical processing of nociception and may constitute an appropriate behavioral tool to assess, monitor, and treat possible pain in brain-damaged noncommunicative patients with disorders of consciousness. Future studies using event-related functional magnetic resonance imaging should investigate the correlation between NCS-R scores and brain activation in response to noxious stimulation at the single-subject level.

Brain dead yet mind alive: A positron emission tomography case study of brain metabolism in Cotard's syndrome

Vanessa Charland-Verville , Marie-Aurelie Bruno , Mohammed Ali Bahri , Athena Demertzi , Martin Desseilles , Camille Chatelle , Audrey Vanhaudenhuyse , Roland Hustinx , Claire Bernard , Luaba Tshibanda , Steven Laureys ** and Adam Zeman * Coma Science Group, Cyclotron Research Center and Neurology Department, CHU Sart-Tilman Hospital and University of Liege, 4000 Liege, Belgium Department of Nuclear Medicine, CHU Sart-Tilman Hospital, University of Liege, Liege, Belgium Department of Radiology, CHU Sart-Tilman Hospital, University of Liege, Liege, Belgium Department of Neurology, Peninsula Medical School, University of Exeter, United Kingdom

Function-structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET.

A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG‐PET metabolism)–structure (MRI‐diffusion‐weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill‐defined. FDG‐PET and MRI‐DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function–structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function–structure relationship was present in brain‐damaged patients between functional metabolism of inferior‐parietal, precuneus, and frontal regions and structural integrity of the frontal‐inferiorparietal, precuneus‐inferiorparietal, thalamo‐inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo‐inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function–structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707–3720, 2016.

FDG PET/CT for rectal carcinoma radiotherapy treatment planning: comparison of functional volume delineation algorithms and clinical challenges.

PET/CT imaging could improve delineation of rectal carcinoma gross tumor volume (GTV) and reduce interobserver variability. The objective of this work was to compare various functional volume delineation algorithms. We enrolled 31 consecutive patients with locally advanced rectal carcinoma. The FDG PET/CT and the high dose CT (CTRT) were performed in the radiation treatment position. For each patient, the anatomical GTVRT was delineated based on the CTRT and compared to six different functional/metabolic GTVPET derived from two automatic segmentation approaches (FLAB and a gradient‐based method); a relative threshold (45% of the SUVmax) and an absolute threshold (SUV>2.5), using two different commercially available software (Philips EBW4 and Segami OASIS). The spatial sizes and shapes of all volumes were compared using the conformity index (CI). All the delineated metabolic tumor volumes (MTVs) were significantly different. The MTVs were as follows (mean±SD):GTVRT(40.6±31.28ml); FLAB(21.36±16.34ml); the gradient‐based method (18.97±16.83ml); OASIS45%(15.89±12.68ml); Philips45%(14.52±10.91ml); OASIS2.5(41.62±33.26ml); Philips2.5(40±31.27ml). CI between these various volumes ranged from 0.40 to 0.90. The mean CI between the different MTVs and the GTVCT was <0.4. Finally, the DICOM transfer of MTVs led to additional volume variations. In conclusion, we observed large and statistically significant variations in tumor volume delineation according to the segmentation algorithms and the software products. The manipulation of PET/CT images and MTVs, such as the DICOM transfer to the Radiation Oncology Department, induced additional volume variations. PACS number: 87.55.D‐

Orthanc - A lightweight, restful DICOM server for healthcare and medical research

Is this paper, the Orthanc open-source software is introduced. Orthanc is a lightweight, yet powerful standalone DICOM store for healthcare and medical research. Multiple instances of Orthanc can easily be deployed in the hospital network or even in the same computer, which simplifies the interconnection between the DICOM modalities and the data management of medical images. Orthanc is unique with respect to the fact that it provides a modern RESTful API: Orthanc can be driven from any computer language to automate clinical processes. Finally, Orthanc comes bundled with an embedded Web interface that allows the end-users to browse and interact with the content of the DICOM store.

Brain plasticity after implanted peroneal nerve electrical stimulation to improve gait in chronic stroke patients: Two case reports

BACKGROUND Recent studies have shown that stimulation of the peroneal nerve using an implantable 4-channel peroneal nerve stimulator could improve gait in stroke patients. OBJECTIVES To assess structural cortical and regional cerebral metabolism changes associated with an implanted peroneal nerve electrical stimulator to correct foot drop related to a central nervous system lesion. METHODS Two stroke patients presenting a foot drop related to a central nervous system lesion were implanted with an implanted peroneal nerve electrical stimulator. Both patients underwent clinical evaluations before implantation and one year after the activation of the stimulator. Structural magnetic resonance imaging (MRI) and [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) were acquired before and one year after the activation of the stimulator. RESULTS Foot drop was corrected for both patients after the implantation of the stimulator. After one year of treatment, patient 1 improved in three major clinical tests, while patient 2 only improved in one test. Prior to treatment, FDG-PET showed a significant hypometabolism in premotor, primary and supplementary motor areas in both patients as compared to controls, with patient 2 presenting more widespread hypometabolism. One year after the activation of the stimulator, both patients showed significantly less hypometabolism in the damaged motor cortex. No difference was observed on the structural MRI. CONCLUSION Clinical improvement of gait under peroneal nerve electrical stimulation in chronic stroke patients presenting foot drop was paralleled to metabolic changes in the damaged motor cortex.