The Virtual Family computational whole-body anatomical human models were originally developed for electromagnetic (EM) exposure evaluations, in particular to study how absorption of radiofrequency radiation from external sources depends on anatomy. However, the models immediately garnered much broader interest and are now applied by over 300 research groups, many from medical applications research fields. In a first step, the Virtual Family was expanded to the Virtual Population to provide considerably broader population coverage with the inclusion of models of both sexes ranging in age from 5 to 84 years old. Although these models have proven to be invaluable for EM dosimetry, it became evident that significantly enhanced models are needed for reliable effectiveness and safety evaluations of diagnostic and therapeutic applications, including medical implants safety. This paper describes the research and development performed to obtain anatomical models that meet the requirements necessary for medical implant safety assessment applications. These include implementation of quality control procedures, re-segmentation at higher resolution, more-consistent tissue assignments, enhanced surface processing and numerous anatomical refinements. Several tools were developed to enhance the functionality of the models, including discretization tools, posing tools to expand the posture space covered, and multiple morphing tools, e.g., to develop pathological models or variations of existing ones. A comprehensive tissue properties database was compiled to complement the library of models. The results are a set of anatomically independent, accurate, and detailed models with smooth, yet feature-rich and topologically conforming surfaces. The models are therefore suited for the creation of unstructured meshes, and the possible applications of the models are extended to a wider range of solvers and physics. The impact of these improvements is shown for the MRI exposure of an adult woman with an orthopedic spinal implant. Future developments include the functionalization of the models for specific physical and physiological modeling tasks.

Traumatic spinal cord injury (SCI) has been shown to trigger structural atrophic changes within the spinal cord and brain. However, the relationship between structural changes and magnitude of neuropathic pain (NP) remains incompletely understood. Voxel-wise analysis of anatomical magnetic resonance imaging data provided information on cross-sectional cervical cord area and volumetric brain changes in 30 individuals with chronic traumatic SCI and 31 healthy controls. Participants were clinically assessed including neurological examination and pain questionnaire. Compared to controls, individuals with SCI exhibited decreased cord area, reduced grey matter (GM) volumes in anterior cingulate cortex (ACC), left insula, left secondary somatosensory cortex, bilateral thalamus, and decreased white matter volumes in pyramids and left internal capsule. The presence of NP was related with smaller cord area, increased GM in left ACC and right M1, and decreased GM in right primary somatosensory cortex and thalamus. Greater GM volume in M1 was associated with amount of NP. Below-level NP-associated structural changes in the spinal cord and brain can be discerned from trauma-induced consequences of SCI. The directionality of these relationships reveals specific changes across the neuroaxis (i.e., atrophic changes versus increases in volume) and may provide substrates of underlying neural mechanisms in the development of NP.

T -weighted scans provided data on the extent and dynamics of neuronal tissue damage and midsagittal tissue bridges at the epicenter of traumatic cervical spinal cord lesions in 24 subacute tetraplegic patients. At 1 month postinjury, smaller lesion area and midsagittal tissue bridges identified those patients with lower extremity evoked potentials and better clinical recovery. Wider midsagittal tissue bridges and smaller lesions at 1 month post-injury were associated with neurological and functional recovery at 1-year follow-up. Neuroimaging biomarkers of lesion size and midsagittal tissue bridges are potential outcome predictors and patient stratifiers in both subacute and chronic clinical trials. Ann Neurol 2017;81:740-748.

ObjectiveTo investigate whether gray matter pathology above the level of injury, alongside white matter changes, also contributes to sensorimotor impairments after spinal cord injury.MethodsA 3T MRI protocol was acquired in 17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used to characterize lesion severity. At the C2-3 level, a high-resolution T2*-weighted sequence was used to assess cross-sectional areas of gray and white matter, including their subcompartments; a diffusion-weighted sequence was used to compute voxel-based diffusion indices. Regression models determined associations between lesion severity and tissue-specific neurodegeneration and associations between the latter with neurophysiologic and clinical outcome.ResultsNeurodegeneration was evident within the dorsal and ventral horns and white matter above the level of injury. Tract-specific neurodegeneration was associated with prolonged conduction of appropriate electrophysiologic recordings. Dorsal horn atrophy was associated with sensory outcome, while ventral horn atrophy was associated with motor outcome. White matter integrity of dorsal columns and corticospinal tracts was associated with daily-life independence.ConclusionOur results suggest that, next to anterograde and retrograde degeneration of white matter tracts, neuronal circuits within the spinal cord far above the level of injury undergo transsynaptic neurodegeneration, resulting in specific gray matter changes. Such improved understanding of tissue-specific cord pathology offers potential biomarkers with more efficient targeting and monitoring of neuroregenerative (i.e., white matter) and neuroprotective (i.e., gray matter) agents.

This study aimed to compare macrostructural and microstructural neurodegenerative changes remote from a cervical spinal cord injury in traumatic spinal cord injury (tSCI) and degenerative cervical myelopathy (DCM) patients using quantitative magnetic resonance imaging (MRI). Twenty-nine tSCI patients, 20 mild/moderate DCM patients, and 22 healthy controls underwent a high-resolution MRI protocol at the cervical cord (C2/C3). High-resolution T2*-weighted and diffusion-weighted scans provided data to calculate tissue-specific cross-sectional areas of the spinal cord and tractspecific diffusion indices of cord white matter, respectively. Regression analysis determined associations between neurodegeneration and clinical impairment. tSCI patients showed more impairment in upper limb strength and manual dexterity when compared with DCM patients. While macrostructural MRI measures revealed a similar extent of remote cord atrophy at cervical level, microstructural measures (diffusion indices) were able to distinguish more pronounced tract-specific neurodegeneration in tSCI patients when compared with DCM patients. Tract-specific neurodegeneration was associated with upper limb impairment. Despite clinical differences between severely impaired tSCI compared with mildly affected DCM patient, extensive cord atrophy is present remotely from the focal spinal cord injury. Diffusion indices revealed greater tract-specific alterations in tSCI patients. Therefore, diffusion indices are more sensitive than macrostructural MRI measures as these are able to distinguish between traumatic and non-traumatic spinal cord injury. Neuroimaging biomarkers of cervical cord integrity hold potential as predictors of recovery and might be suitable biomarkers for interventional trials both in traumatic and non-traumatic SCI.

Rapidly repeated imaging of the left middle fingertip skin blood perfusion was performed in 51 healthy volunteers (mean age +/- SD: 25.3 +/- 7.6 years) prior to, immediately after and in the early reperfusion phase following introduction of an acupuncture needle at the Neiguan point (Pe. 6) and at a placebo point respectively, using a Laser Doppler Perfusion Imager (LDPI). The average skin perfusion of the fingertip was calculated for each image and used as an indicator of the microvascular response to the acupuncture needle introduction. The results of this randomised, placebo-controlled, cross-over study showed significant differences (p < or = 0.001) in the immediate skin blood perfusion response when needling is performed in an acupuncture point (Neiguan) and a placebo point, with a more pronounced reduction in skin blood perfusion when needling the acupuncture point. In the early reperfusion phase, however, a substantial increase in skin perfusion was observed that amounted to about 18% of the level prior to needle introduction, irrespective of the site of needle application. In a single individual it was demonstrated that the vasodilatation following needling in the acupuncture point persisted for a more extended time period. These results suggest that the LDPI technology may be useful in visualising and quantifying the peripheral vascular effects of acupuncture on the microcirculation.

ObjectiveTo investigate the spatiotemporal evolution and predictive properties of intramedullary damage and midsagittal tissue bridges at the epicenter of a thoracic spinal cord injury (SCI) using MRI.MethodsWe retrospectively assessed midsagittal T2-weighted scans from 25 patients with thoracic SCI (14 traumatic, 11 ischemic) at 1 month post-SCI. In 12 patients with SCI, linear mixed-effects models on serial MRI explored temporal trajectories of quantifiable lesion markers (area, length, and width) and tissue bridges. Using partial correlation analysis, we assessed associations between structural lesion characteristics at 1 month post-SCI and recovery at 1 year postinjury, adjusting for baseline clinical status, age, and sex.ResultsLesion area decreased by 5.68 mm2 (p = 0.005), lesion length by 2.14 mm (p = 0.004), and lesion width by 0.13 mm (p = 0.004) per month. Width of tissue bridges increased by 0.06 mm (p = 0.019) per month, being similar in traumatic and ischemic SCI (p = 0.576). Smaller lesion area, length, width, and wider tissue bridges at 1 month post-SCI predicted better recovery at 1-year follow-up.ConclusionsOver time, the immediate area of cord damage shrunk while the cystic cavity became demarcated. Adjacent to the cyst, midsagittal tissue bridges became visible. The width of tissue bridges at 1 month post-SCI predicted recovery at 1 year follow-up. Measures of lesion area and tissue bridges early after traumatic and ischemic thoracic SCI therefore allow characterizing the evolution of focal cord damage and are predictive of recovery in thoracic SCI. Thus, lesion extent and tissue bridges hold potential to improve diagnosis and patient stratification in interventional trials.

ObjectiveTo assess whether preserved dorsal and ventral midsagittal tissue bridges after traumatic cervical spinal cord injury (SCI) encode tract-specific electrophysiologic properties and are predictive of appropriate recovery.MethodsIn this longitudinal study, we retrospectively assessed MRI scans at 1 month after SCI that provided data on width and location (dorsal vs ventral) of midsagittal tissue bridges in 28 tetraplegic patients. Regression analysis assessed associations between midsagittal tissue bridges and motor- and sensory-specific electrophysiologic recordings and appropriate outcome measures at 12 months after SCI.ResultsGreater width of dorsal midsagittal tissue bridges at 1 month after SCI identified patients who were classified as being sensory incomplete at 12 months after SCI (p = 0.025), had shorter sensory evoked potential (SEP) latencies (r = −0.57, p = 0.016), and had greater SEP amplitudes (r = 0.61, p = 0.001). Greater width of dorsal tissue bridges predicted better light-touch score at 12 months (r = 0.40, p = 0.045) independently of baseline clinical score and ventral tissue bridges. Greater width of ventral midsagittal tissue bridges at 1 month identified patients who were classified as being motor incomplete at 12 months (p = 0.002), revealed shorter motor evoked potential (MEP) latencies (r = −0.54, p = 0.044), and had greater ratios of MEP amplitude to compound muscle action potential amplitude (r = 0.56, p = 0.005). Greater width of ventral tissue bridges predicted better lower extremity motor scores at 12 months (r = 0.41, p = 0.035) independently of baseline clinical score and dorsal tissue bridges.ConclusionMidsagittal tissue bridges, detectable early after SCI, underwrite tract-specific electrophysiologic communication and are predictors of appropriate sensorimotor recovery. Neuroimaging biomarkers of midsagittal tissue bridges may be integrated into the diagnostic workup, prediction of recovery, and patients' stratification in clinical trials.