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Intracranial Effects of Artificial Gravity: A 3T MRI Study

INTRODUCTION Spaceflight associated neuro-ocular syndrome (SANS) is characterized by the development of optic disc edema, posterior globe flattening, choroidal/retinal folds and hyperopic refractive errors1. SANS is hypothesized to be a result of headward fluid shifts that invariably occurs in the microgravity environment. As a countermeasure, artificial gravity (AG) through centrifugation has been proposed to reduce this headward fluid shift, however there is no current proof of benefit. The goal of this study was to determine if the application of AG can prevent or reduce known changes in brain volumetry, internal carotid artery (ICA) stroke volume and cerebral spinal fluid (CSF) flow velocity that occurs during simulated chronic headward fluid shift using head down tilt bed rest (HDTBR) methodology2 as an indicator of countermeasure efficacy. METHODS Healthy volunteers were recruited for an IRB approved HDTBR study performed at the German Aerospace Center in Cologne, Germany. Strict six-degree HDTBR was used as a spaceflight analog to induce a continuous headward fluid shift. HDTBR was carried out for 60 days for all subjects. Short-arm centrifugation was utilized to generate AG equating to ~0.3g of acceleration at the level of the eye. The subjects were divided equally into three groups: NoAG (control; n=8), daily intermittent AG (6 x 5 min iAG; n=8), and daily continuous 30 min (cAG; n=8). All studies were performed on a single dedicated 3T MRI Scanner. Pulse-gated MRI phase-contrast flow imaging was used to quantify ICA stroke volume and peak-to-peak CSF flow velocity in the mid cerebral aqueduct. 3D-SPGR was acquired for volumetric segmentation of the brain and CSF spaces. MRI acquisitions were obtained at baseline (BDC), 14 days into HDTBR (HDTBR14), 52 days into HDTBR (HDTBR52) and 3-5 days after HDTBR (recovery, R+3/5).The data were analyzed by the mixed model, which included intervention and time (BDC, HDTBR 14, HDTBR 52, R+3/5) as the fixed effects and included subject as the random effect.RESULTS24 healthy subject volunteers (16 men, 8 women, mean age = 33 years ± 9 [standard deviation] and mean BMI = 24.3 kg/m2 ± 2.0) successfully completed all phases of the study. Strict six-degree HDTBR was characterized by progressive and statistically significant (p<.01) increases in mean combined brain and CSF volumes and mean aqueductal CSF peak-to-peak flow velocity, as well as statistically significant (p<.01) progressive decrease in mean ICA stroke volume from baseline to 52 days post intervention (Figs. 1-3). Compared to baseline, only combined brain and CSF volumes did not return to baseline values in the recovery period (p=NS). Neither iAG nor cAG exerted any significant effects on the measured MRI brain parameters as compared to HDTBR alone (p=NS). CONCLUSION Our results indicate that HDTBR at 6-degrees was effective in producing alterations in ICA stroke volume, aqueductal CSF flow velocity, and combined brain and CSF volumetric change that is associated with chronic headward fluid shift. Short duration, 30-min daily exposure to either iAG or cAG appears to be insufficient in preventing or reducing the effects of chronic HDTBR and thus may not be a suitable countermeasure as currently deployed. AG protocol modifications, including increased duration and magnitude of exposure, should be considered for future research.

L A Kramer

A semi-automatic method for left ventricle volume estimate: an in vivo validation study

This study aims to the validation of the left ventricular (LV) volume estimates obtained by processing volumetric data utilizing a segmentation model based on level set technique. The validation has been performed by comparing real-time volumetric echo data (RT3DE) and magnetic resonance (MRI) data. A validation protocol has been defined. The validation protocol was applied to twenty-four estimates (range 61-467 ml) obtained from normal and pathologic subjects, which underwent both RT3DE and MRI. A statistical analysis was performed on each estimate and on clinical parameters as stroke volume (SV) and ejection fraction (EF). Assuming MRI estimates (x) as a reference, an excellent correlation was found with volume measured by utilizing the segmentation procedure (y) (y=0.89x + 13.78, r=0.98). The mean error on SV was 8 ml and the mean error on EF was 2%. This study demonstrated that the segmentation technique is reliably applicable on human hearts in clinical practice.

NASA Discipline Cardiopulmonary

Brain segmentation and the generation of cortical surfaces

This paper describes methods for white matter segmentation in brain images and the generation of cortical surfaces from the segmentations. We have developed a system that allows a user to start with a brain volume, obtained by modalities such as MRI or cryosection, and constructs a complete digital representation of the cortical surface. The methodology consists of three basic components: local parametric modeling and Bayesian segmentation; surface generation and local quadratic coordinate fitting; and surface editing. Segmentations are computed by parametrically fitting known density functions to the histogram of the image using the expectation maximization algorithm [DLR77]. The parametric fits are obtained locally rather than globally over the whole volume to overcome local variations in gray levels. To represent the boundary of the gray and white matter we use triangulated meshes generated using isosurface generation algorithms [GH95]. A complete system of local parametric quadratic charts [JWM+95] is superimposed on the triangulated graph to facilitate smoothing and geodesic curve tracking. Algorithms for surface editing include extraction of the largest closed surface. Results for several macaque brains are presented comparing automated and hand surface generation. Copyright 1999 Academic Press.

NASA Discipline Neuroscience

Automated Cardiovascular Pathology Assessment using Semantic Segmentation and Ensemble Learning

Cardiac magnetic resonance imaging provides high spatial resolution, enabling improved extraction of important functional and morphological features for cardiovascular disease staging. Segmentation of ventricular cavities and myocardium in cardiac cine sequencing provides a basis to quantify cardiac measures such as ejection fraction. A method is presented that curtails the expense and observer bias of manual cardiac evaluation by combining semantic segmentation and disease classification into a fully automatic processing pipeline. The initial processing element consists of a robust dilated convolutional neural network architecture for voxel-wise segmentation of the myocardium and ventricular cavities. The resulting comprehensive volumetric feature matrix captures diagnostic clinical procedure data and is utilized by the final processing element to model a cardiac pathology classifier. Our approach evaluated anonymized cardiac images from a training data set of 100 patients (4 pathology groups, 1 healthy group, 20 patients per group) examined at the University Hospital of Dijon. The top average Dice index scores achieved were 0.940, 0.886, 0.849 for structure segmentation of the left ventricle (LV), myocardium and right ventricle (RV) respectively. A 5-ary pathology classification accuracy of 90% was recorded on an independent test set using the trained model. Performance results demonstrate potential for advanced machine learning methods to deliver accurate, efficient and reproducible cardiac pathological assessment.

Semantic Segmentation

Automated Semantic Segmentation for Volumetric Cardiovascular Feature Quantification and Pathology Assessment

We present a pipeline method that curtails the expense and observer bias of manual cardiac evaluation by combining semantic segmentation and disease classification as a fully automatic processing pipeline. The initial element consists of a 2D U-Net convolutional neural network architecture for voxel-wise segmentation of the myocardium and ventricular cavities. The results of the segmentation were used to compute a comprehensive volumetric feature matrix that captured diagnostic clinical procedure data and that was used to model a cardiac pathology classifier.Our approach evaluated anonymized parasternal MRI cardiac images from a database of 100 patients (4 pathology groups, 1 healthy group, 20 patients per group) examined at the University Hospital of Dijon. We achieved top average Dice index scores of 0.939, 0.849, 0.886 for structure segmentation of the left ventricle (LV), right ventricle (RV) and myocardium respectively. A 5-ary pathology classification accuracy of 90% was recorded on an independent test set using our trained model.

Lindsey, Tony

Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed in a subject with VIIP signs. Study limitations include a slightly longer landing-to-MRI scan period for the short-duration cohort and limited sensitivity of the subjective discrete ordinal CPG scale. This limitation can be overcome by using imaging based parametric measures of VIIP severity such as globe deformation measures.

Alperin, Noam

High resolution magnetic resonance imaging of the calcaneus: age-related changes in trabecular structure and comparison with dual X-ray absorptiometry measurements

A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 +/- 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1-2% and 3-6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r2 = 33.7%, P < 0.0037), I.Th (r2 = 26.6%, P < 0.0118), I.Sp (r2 = 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (-0.52%/year), I.Th (-0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure.

NASA Discipline Number 26-10

Focal Gray Matter Plasticity as a Function of Long Duration Head Down Tilted Bed Rest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes are solely related to peripheral changes from reduced vestibular stimulation, body unloading, body fluid shifts or that they may be related to structural and functional brain changes is yet unknown. However, a recent study reported associations between microgravity and flattening of the posterior eye globe and protrusion of the optic nerve [1] possibly as the result of increased intracranial pressure due to microgravity induced bodily fluid shifts [3]. Moreover, elevated intracranial pressure has been related to white matter microstructural damage [2]. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning. Long duration head down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system [4]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on brain structure [5]. Here we present results of the first six subjects. Six subjects were assessed at 12 and 7 days before-, at 7, 30, and ~70 days in-, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility in UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1-weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Longitudinal processing in VBM8 includes linear registration of each scan to the mean of the subject and subsequently transforming all scans in to MNI space by applying the warp from the mean subject to MNI to the individual gray matter segmentations. Modulation was applied so that all images represented the volume of the original structure in native space. Voxel wise analysis was carried out on the gray matter images after smoothing, using a flexible factorial design with family wise error correction. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. For each subject, for each DTI metric (i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)), the maximum value in a line perpendicular to the skeleton tract is projected to the skeleton. Non-parametric permutation based t-tests and ANOVA's were used for voxel-wise comparison of the skeletons. For both VBM and TBSS, comparison of pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate (see Figure) from 'pre to in bed rest'. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital-, and parietal cortex, including the precuneus (see Figure). The majority of these changes did not recover from 'during to post bed rest'. TBSS analysis did not reveal significant changes in white matter microstructural integrity after correction for multiple comparisons. Uncorrected analyses (p<.015) revealed an increase in RD in the cerebellum and brainstem from pre bed rest to the first week in bed rest that did not recover post bed rest. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuro motor behavior and cognition. These changes did not recover at two weeks post bed rest. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.

Hierarchical Segmentation Enhances Diagnostic Imaging

Bartron Medical Imaging LLC (BMI), of New Haven, Connecticut, gained a nonexclusive license from Goddard Space Flight Center to use the RHSEG software in medical imaging. To manage image data, BMI then licensed two pattern-matching software programs from NASA's Jet Propulsion Laboratory that were used in image analysis and three data-mining and edge-detection programs from Kennedy Space Center. More recently, BMI made NASA history by being the first company to partner with the Space Agency through a Cooperative Research and Development Agreement to develop a 3-D version of RHSEG. With U.S. Food and Drug Administration clearance, BMI will sell its Med-Seg imaging system with the 2-D version of the RHSEG software to analyze medical imagery from CAT and PET scans, MRI, ultrasound, digitized X-rays, digitized mammographies, dental X-rays, soft tissue analyses, moving object analyses, and soft-tissue slides such as Pap smears for the diagnoses and management of diseases. Extending the software's capabilities to three dimensions will eventually enable production of pixel-level views of a tumor or lesion, early identification of plaque build-up in arteries, and identification of density levels of microcalcification in mammographies.

Source record

VIIP 2017 Clinical Update

INTRODUCTION: NASA's Space Medicine community knowledge regarding the "Vision Impairment Intracranial Pressure", or VIIP.has been evolving over time.. Various measures of occupational health related to this condition had to be determined and then plans/processes put into place. The most robust of these processes were inititated in 2010. This presentation will provide a clinic update of the astronaut occupational health data related to VIIP. METHODS: NASA and its international partners require its astronauts to undergo routine health measures deemed important to monitoring VIIP. The concern is that the spaceflight environment aboard ISS could cause some astronauts to have physiologic changes detrimental to either ongoing mission operations or long-term health related to the ocular system and possibly the CNS. Specific medical tests include but are not limited to brain/orbit MRI (NASA unique protocol), OCT, fundoscopy and ocular ultrasound. Measures are taken prior to spaceflight, in-flight and post-flight. Measures to be reported include incidence of disc edema, globe flattening, choroidal folds, ONSD and change in refractive error. RESULTS: 73 ISS astronauts have been evaluated at least partially for VIIP related measures. Of these individuals, approximately 1 in 7 have experienced disc edema. The prevalence of the other findings is more complicated as the medical testing has changed over time. Overall, 26 separate individuals have experienced at least one of the findings NASA has associated with VIIP Another confounding factor is most of the astronauts have prior spaceflight experience at the time of the "pre-flight" testing. DISCUSSION: In 2010 NASA and its US operating segment (USOS) partners (CSA, ESA and JAXA) began routine occupational monitoring and data collection for most VIIP related changes. Interpretation of that data is extremely challenging for several reasons. For example, the determination of disc edema is the most complete finding as we have had highly qualified optometrists routinely and competently performing post-flight funduscopic exams for the entirety of the ISS program. Yet in 2013 NASA added OCT to our in-flight suite of eye exams. Shortly after routine screening with the OCT, a new term appeared within VIIP vernacular - "subclinical disc edema". OCT has much greater ability to measure change within the retina and provides significantly more data to analyze, understand and communicate out. Communicating VIIP data clearly adds even more challenge. Historically we've reported data per eye and not necessarily per person. This has led to difficulty in understanding how many individuals have experienced "VIIP" within the aerospace medicine community. The presenter will attempt to provide clear and concise communication of VIIP findings.

Tarver, William