Water Diffusion in the Live Human Brain is Gaussian at the Mesoscale.

Imaging the live human brain at the mesoscopic scale is a desideratum in basic and clinical neurosciences. Despite the promise of diffusion MRI, the lack of an accurate model relating the measured signal and the associated microstructure has hampered its success. The widely used diffusion tensor MRI (DTI) model assumes an anisotropic Gaussian diffusion process in each voxel, but lacks the ability to capture intravoxel heterogeneity. This study explores the extension of the DTI model to mesoscopic length scales by use of the diffusion tensor distribution (DTD) model, which assumes a Gaussian diffusion process in each subvoxel. DTD MRI has shown promise in addressing some limitations of DTI, particularly in distinguishing among different types of brain cancers and elucidating multiple fiber populations within a voxel. However, its validity in live brain tissue has never been established. Here, multiple diffusion-encoded (MDE) data were acquired in the living human brain using a 3 Tesla MRI scanner with large diffusion weighting factors. Two different diffusion times (Δ = 37, 74 ms) were employed, with other scanning parameters fixed to assess signal decay differences. In vivo diffusion-weighted signals in gray and white matter were nearly identical at the two diffusion times. Fitting the signals to the DTD model yielded indistinguishable results, except in the cerebrospinal fluid (CSF)-filled voxels likely due to pulsatile flow. Overall, the study supports the time invariance of water diffusion at the mesoscopic scale in live brain parenchyma, extending the validity of the anisotropic Gaussian diffusion model in clinical brain imaging.

The Subcortical Atlas of the Marmoset ("SAM") monkey based on high-resolution MRI and histology.

A comprehensive three-dimensional digital brain atlas of cortical and subcortical regions based on MRI and histology has a broad array of applications in anatomical, functional, and clinical studies. We first generated a Subcortical Atlas of the Marmoset, called the "SAM," from 251 delineated subcortical regions (e.g. thalamic subregions, etc.) derived from high-resolution Mean Apparent Propagator-MRI, T2W, and magnetization transfer ratio images ex vivo. We then confirmed the location and borders of these segmented regions in the MRI data using matched histological sections with multiple stains obtained from the same specimen. Finally, we estimated and confirmed the atlas-based areal boundaries of subcortical regions by registering this ex vivo atlas template to in vivo T1- or T2W MRI datasets of different age groups (single vs. multisubject population-based marmoset control adults) using a novel pipeline developed within Analysis of Functional NeuroImages software. Tracing and validating these important deep brain structures in 3D will improve neurosurgical planning, anatomical tract tracer injections, navigation of deep brain stimulation probes, functional MRI and brain connectivity studies, and our understanding of brain structure-function relationships. This new ex vivo template and atlas are available as volumes in standard NIFTI and GIFTI file formats and are intended for use as a reference standard for marmoset brain research.

The Subcortical Atlas of the Marmoset ("SAM") monkey based on high-resolution MRI and histology.

A comprehensive three-dimensional digital brain atlas of cortical and subcortical regions based on MRI and histology has a broad array of applications for anatomical, functional, and clinical studies. We first generated a Subcortical Atlas of the Marmoset, called the "SAM," from 251 delineated subcortical regions (e.g., thalamic subregions, etc.) derived from the high-resolution MAP-MRI, T2W, and MTR images ex vivo. We then confirmed the location and borders of these segmented regions in MRI data using matched histological sections with multiple stains obtained from the same specimen. Finally, we estimated and confirmed the atlas-based areal boundaries of subcortical regions by registering this ex vivo atlas template to in vivo T1- or T2W MRI datasets of different age groups (single vs. multisubject population-based marmoset control adults) using a novel pipeline developed within AFNI. Tracing and validating these important deep brain structures in 3D improves neurosurgical planning, anatomical tract tracer injections, navigation of deep brain stimulation probes, fMRI and brain connectivity studies, and our understanding of brain structure-function relationships. This new ex vivo template and atlas are available as volumes in standard NIFTI and GIFTI file formats and are intended for use as a reference standard for marmoset brain research.

Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae.

Despite enabling Streptococcus pneumoniae to acquire antibiotic resistance and evade vaccine-induced immunity, transformation occurs at variable rates across pneumococci. Phase variants of isolate RMV7, distinguished by altered methylation patterns driven by the translocating variable restriction-modification (tvr) locus, differed significantly in their transformation efficiencies and biofilm thicknesses. These differences were replicated when the corresponding tvr alleles were introduced into an RMV7 derivative lacking the locus. RNA-seq identified differential expression of the type 1 pilus, causing the variation in biofilm formation, and inhibition of competence induction in the less transformable variant, RMV7domi. This was partly attributable to RMV7domi's lower expression of ManLMN, which promoted competence induction through importing N-acetylglucosamine. This effect was potentiated by analogues of some proteobacterial competence regulatory machinery. Additionally, one of RMV7domi's phage-related chromosomal island was relatively active, which inhibited transformation by increasing expression of the stress response proteins ClpP and HrcA. However, HrcA increased competence induction in the other variant, with its effects depending on Ca2+ supplementation and heat shock. Hence the heterogeneity in transformation efficiency likely reflects the diverse signalling pathways by which it is affected. This regulatory complexity will modulate population-wide responses to synchronising quorum sensing signals to produce co-ordinated yet stochastic bet hedging behaviour.

Multimodal anatomical mapping of subcortical regions in marmoset monkeys using high-resolution MRI and matched histology with multiple stains.

Subcortical nuclei and other deep brain structures play essential roles in regulating the central and peripheral nervous systems. However, many of these nuclei and their subregions are challenging to identify and delineate in conventional MRI due to their small size, hidden location, and often subtle contrasts compared to neighboring regions. To address these limitations, we scanned the whole brain of the marmoset monkeys in ex vivo using a clinically feasible diffusion MRI method, called the mean apparent propagator (MAP)-MRI, along with T2W and MTR (T1-like contrast) images acquired at 7 Tesla. Additionally, we registered these multimodal MRI volumes to the high-resolution images of matched whole-brain histology sections with seven different stains obtained from the same brain specimens. At high spatial resolution, the microstructural parameters and fiber orientation distribution functions derived with MAP-MRI can distinguish the subregions of many subcortical and deep brain structures, including fiber tracts of different sizes and orientations. The good correlation with multiple but distinct histological stains from the same brain serves as a thorough validation of the structures identified with MAP-MRI and other MRI parameters. Moreover, the anatomical details of deep brain structures found in the volumes of MAP-MRI parameters are not visible in conventional T1W or T2W images. The high-resolution mapping using novel MRI contrasts, combined and correlated with histology, can elucidate structures that were previously invisible radiologically. Thus, this multimodal approach offers a roadmap toward identifying salient brain areas in vivo in future neuroradiological studies. It also provides a useful anatomical standard reference for the region definition of subcortical targets and the generation of a 3D digital template atlas for the marmoset brain research (Saleem et al., 2023). Additionally, we conducted a cross-species comparison between marmoset and macaque monkeys using results from our previous studies (Saleem et al., 2021). We found that the two species had distinct patterns of iron distribution in subregions of the basal ganglia, red nucleus, and deep cerebellar nuclei, confirmed with T2W MRI and histology.

Multimodal anatomical mapping of subcortical regions in Marmoset monkeys using high-resolution MRI and matched histology with multiple stains.

Subcortical nuclei and other deep brain structures play essential roles in regulating the central and peripheral nervous systems. However, many of these nuclei and their subregions are challenging to identify and delineate in conventional MRI due to their small size, hidden location, and often subtle contrasts compared to neighboring regions. To address these limitations, we scanned the whole brain of the marmoset monkeys in ex vivo using a clinically feasible diffusion MRI method, called the mean apparent propagator (MAP)-MRI, along with T2W and MTR (T1-like contrast) images acquired at 7 Tesla. Additionally, we registered these multimodal MRI volumes to the high-resolution images of matched whole-brain histology sections with seven different stains obtained from the same brain specimens. At high spatial resolution, the microstructural parameters and fiber orientation distribution functions derived with MAP-MRI can distinguish the subregions of many subcortical and deep brain structures, including fiber tracts of different sizes and orientations. The good correlation with multiple but distinct histological stains from the same brain serves as a thorough validation of the structures identified with MAP-MRI and other MRI parameters. Moreover, the anatomical details of deep brain structures found in the volumes of MAP-MRI parameters are not visible in conventional T1W or T2W images. The high-resolution mapping using novel MRI contrasts, combined and correlated with histology, can elucidate structures that were previously invisible radiologically. Thus, this multimodal approach offers a roadmap toward identifying salient brain areas in vivo in future neuroradiological studies. It also provides a useful anatomical standard reference for the region definition of subcortical targets and the generation of a 3D digital template atlas for the marmoset brain research (Saleem et al., 2023). Additionally, we conducted a cross-species comparison between marmoset and macaque monkeys using results from our previous studies (Saleem et al., 2021). We found that the two species had distinct patterns of iron distribution in subregions of the basal ganglia, red nucleus, and deep cerebellar nuclei, confirmed with T2W MRI and histology.

A novel framework for in-vivo diffusion tensor distribution MRI of the human brain.

Neural tissue microstructure plays an important role in developmental, physiological and pathophysiological processes. Diffusion tensor distribution (DTD) MRI helps probe subvoxel heterogeneity by describing water diffusion within a voxel using an ensemble of non-exchanging compartments characterized by a probability density function of diffusion tensors. In this study, we provide a new framework for acquiring multiple diffusion encoding (MDE) images and estimating DTD from them in the human brain in vivo. We interfused pulsed field gradients (iPFG) in a single spin echo to generate arbitrary b-tensors of rank one, two, or three without introducing concomitant gradient artifacts. Employing well-defined diffusion encoding parameters we show that iPFG retains salient features of a traditional multiple-PFG (mPFG/MDE) sequence while reducing the echo time and coherence pathway artifacts thereby extending its applications beyond DTD MRI. Our DTD is a maximum entropy tensor-variate normal distribution whose tensor random variables are constrained to be positive definite to ensure their physicality. In each voxel, the second-order mean and fourth-order covariance tensors of the DTD are estimated using a Monte Carlo method that synthesizes micro-diffusion tensors with corresponding size, shape, and orientation distributions to best fit the measured MDE images. From these tensors we obtain the spectrum of diffusion tensor ellipsoid sizes and shapes, and the microscopic orientation distribution function (µODF) and microscopic fractional anisotropy (µFA) that disentangle the underlying heterogeneity within a voxel. Using the DTD-derived µODF, we introduce a new method to perform fiber tractography capable of resolving complex fiber configurations. The results revealed microscopic anisotropy in various gray and white matter regions and skewed MD distributions in cerebellar gray matter not observed previously. DTD MRI tractography captured complex white matter fiber organization consistent with known anatomy. DTD MRI also resolved some degeneracies associated with diffusion tensor imaging (DTI) and elucidated the source of diffusion heterogeneity which may help improve the diagnosis of various neurological diseases and disorders.

Adult lifespan maturation and degeneration patterns in gray and white matter: A mean apparent propagator (MAP) MRI study.

The relationship between brain microstructure and aging has been the subject of intense study, with diffusion MRI perhaps the most effective modality for elucidating these associations. Here, we used the mean apparent propagator (MAP)-MRI framework, which is suitable to characterize complex microstructure, to investigate age-related cerebral differences in a cohort of cognitively unimpaired participants and compared the results to those derived using diffusion tensor imaging. We studied MAP-MRI metrics, among them the non-Gaussianity (NG) and propagator anisotropy (PA), and established an opposing pattern in white matter of higher NG alongside lower PA among older adults, likely indicative of axonal degradation. In gray matter, however, these two indices were consistent with one another, and exhibited regional pattern heterogeneity compared to other microstructural parameters, which could indicate fewer neuronal projections across cortical layers along with an increased glial concentration. In addition, we report regional variations in the magnitude of age-related microstructural differences consistent with the posterior-anterior shift in aging paradigm. These results encourage further investigations in cognitive impairments and neurodegeneration.

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA.

BACKGROUND: The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180). METHODS: A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain's evolution. RESULTS: GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage ϕOXC141. Prior to the introduction of PCV13, this clade's composition shifted towards a ϕOXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also ϕOXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the ~100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage ϕOXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in ~30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation. CONCLUSION: This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics.

High-resolution cortical MAP-MRI reveals areal borders and laminar substructures observed with histological staining.

The variations in cellular composition and tissue architecture measured with histology provide the biological basis for partitioning the brain into distinct cytoarchitectonic areas and for characterizing neuropathological tissue alterations. Clearly, there is an urgent need to develop whole-brain neuroradiological methods that can assess cortical cyto- and myeloarchitectonic features non-invasively. Mean apparent propagator (MAP) MRI is a clinically feasible diffusion MRI method that quantifies efficiently and comprehensively the net microscopic displacements of water molecules diffusing in tissues. We investigate the sensitivity of high-resolution MAP-MRI to detecting areal and laminar variations in cortical cytoarchitecture and compare our results with observations from corresponding histological sections in the entire brain of a rhesus macaque monkey. High-resolution images of MAP-derived parameters, in particular the propagator anisotropy (PA), non-gaussianity (NG), and the return-to-axis probability (RTAP) reveal cortical area-specific lamination patterns in good agreement with the corresponding histological stained sections. In a few regions, the MAP parameters provide superior contrast to the five histological stains used in this study, delineating more clearly boundaries and transition regions between cortical areas and laminar substructures. Throughout the cortex, various MAP parameters can be used to delineate transition regions between specific cortical areas observed with histology and to refine areal boundaries estimated using atlas registration-based cortical parcellation. Using surface-based analysis of MAP parameters we quantify the cortical depth dependence of diffusion propagators in multiple regions-of-interest in a consistent and rigorous manner that is largely independent of the cortical folding geometry. The ability to assess cortical cytoarchitectonic features efficiently and non-invasively, its clinical feasibility, and translatability make high-resolution MAP-MRI a promising 3D imaging tool for studying whole-brain cortical organization, characterizing abnormal cortical development, improving early diagnosis of neurodegenerative diseases, identifying targets for biopsies, and complementing neuropathological investigations.

Identifying transcranial magnetic stimulation induced EEG signatures of different neuronal elements in primary motor cortex.

OBJECTIVE: To investigate the neuronal elements involved in the activation of corticospinal neurons in the primary motor cortex (M1). METHODS: We studied 10 healthy subjects. Cortical evoked potentials with different components induced by monophasic transcranial magnetic stimulation (TMS) in anterior-posterior and posterior-anterior currents recorded with electroencephalography (EEG) were analyzed. RESULTS: EEG signatures with P25 and N45 components recorded at the C3 electrode with posterior-anterior current were larger than those with anterior-posterior current, while the signatures with P180 and N280 components recorded at the FC1 electrode with anterior-posterior current were larger than those with posterior-anterior current. The source localization analysis revealed that the cortical evoked potential with anterior-posterior current distributed both in the M1 and premotor cortex while that with posterior-anterior current only located in the M1. CONCLUSIONS: We conclude that the activation of corticospinal pyramidal neurons in the M1 is affected by various neuronal elements including the local intracortical circuits in the M1 and inputs from premotor cortex with different sensitivities to TMS in opposite current directions. SIGNIFICANCE: Our finding helped answer a longstanding question about how the corticospinal pathway from the M1 is functionally organized and activated.

Minimising donor-site morbidity following limbs' injuries with keystone perforator island flap reconstruction.

Plastic surgeons strive to choose better techniques to reconstruct the defects of the limbs, minimising the wound healing problems, improving the aesthetic and functional outcome with less complications. This study refers to the use of keystone perforator island flap (KPIF) in limbs' reconstruction, their harvesting technique to minimise donor-site morbidity, maximise the functional and cosmetic outcome, and will point on the most important indications and advantages. Between January 2014 and June 2020, a number of 28 cases were treated in our department, with simple or complex defects of the limbs. The database included patients' demographics, comorbidities, aetiology, characteristics of the flap, surgical factors, follow-up period and flap outcomes. We performed 28 KPIFs, 14 of type I, 12 of type IIA, 1 of type III, and 1 of type IV, with an average size of 69 cm2 (ranged from 1.25 cm2 to 318 cm2 ). Trauma was the major cause of the defects. One flap exhibited approximately 4% partial superficial necrosis. All donor sites healed without any adverse events. All patients were satisfied with the functional and aesthetic results. The KPIFs provide a simple and effective method of wound closure by using tissues of similar texture, thickness and colour. Preserving the main artery and the underlying muscle, this flap reduces the donor site morbidity. The use of KPIFs seems to be one of the most suitable choices whenever possible.

COnstrained Reference frame diffusion TEnsor Correlation Spectroscopic (CORTECS) MRI: A practical framework for high-resolution diffusion tensor distribution imaging.

High-resolution imaging studies have consistently shown that in cortical tissue water diffuses preferentially along radial and tangential orientations with respect to the cortical surface, in agreement with histology. These dominant orientations do not change significantly even if the relative contributions from microscopic water pools to the net voxel signal vary across experiments that use different diffusion times, b-values, TEs, and TRs. With this in mind, we propose a practical new framework for imaging non-parametric diffusion tensor distributions (DTDs) by constraining the microscopic diffusion tensors of the DTD to be diagonalized using the same orthonormal reference frame of the mesoscopic voxel. In each voxel, the constrained DTD (cDTD) is completely determined by the correlation spectrum of the microscopic principal diffusivities associated with the axes of the voxel reference frame. Consequently, all cDTDs are inherently limited to the domain of positive definite tensors and can be reconstructed efficiently using Inverse Laplace Transform methods. Moreover, the cDTD reconstruction can be performed using only data acquired efficiently with single diffusion encoding, although it also supports datasets with multiple diffusion encoding. In tissues with a well-defined architecture, such as the cortex, we can further constrain the cDTD to contain only cylindrically symmetric diffusion tensors and measure the 2D correlation spectra of principal diffusivities along the radial and tangential orientation with respect to the cortical surface. To demonstrate this framework, we perform numerical simulations and analyze high-resolution dMRI data from a fixed macaque monkey brain. We estimate 2D cDTDs in the cortex and derive, in each voxel, the marginal distributions of the microscopic principal diffusivities, the corresponding distributions of the microscopic fractional anisotropies and mean diffusivities along with their 2D correlation spectra to quantify the cDTD shape-size characteristics. Signal components corresponding to specific bands in these cDTD-derived spectra show high specificity to cortical laminar structures observed with histology. Our framework drastically simplifies the measurement of non-parametric DTDs in high-resolution datasets with mesoscopic voxel sizes much smaller than the radius of curvature of the underlying anatomy, e.g., cortical surface, and can be applied retrospectively to analyze existing diffusion MRI data from fixed cortical tissues.

High-resolution mapping and digital atlas of subcortical regions in the macaque monkey based on matched MAP-MRI and histology.

Subcortical nuclei and other deep brain structures are known to play an important role in the regulation of the central and peripheral nervous systems. It can be difficult to identify and delineate many of these nuclei and their finer subdivisions in conventional MRI due to their small size, buried location, and often subtle contrast compared to neighboring tissue. To address this problem, we applied a multi-modal approach in ex vivo non-human primate (NHP) brain that includes high-resolution mean apparent propagator (MAP)-MRI and five different histological stains imaged with high-resolution microscopy in the brain of the same subject. By registering these high-dimensional MRI data to high-resolution histology data, we can map the location, boundaries, subdivisions, and micro-architectural features of subcortical gray matter regions in the macaque monkey brain. At high spatial resolution, diffusion MRI in general, and MAP-MRI in particular, can distinguish a large number of deep brain structures, including the larger and smaller white matter fiber tracts as well as architectonic features within various nuclei. Correlation with histology from the same brain enables a thorough validation of the structures identified with MAP-MRI. Moreover, anatomical details that are evident in images of MAP-MRI parameters are not visible in conventional T1-weighted images. We also derived subcortical template "SC21" from segmented MRI slices in three-dimensions and registered this volume to a previously published anatomical template with cortical parcellation (Reveley et al., 2017; Saleem and Logothetis, 2012), thereby integrating the 3D segmentation of both cortical and subcortical regions into the same volume. This newly updated three-dimensional D99 digital brain atlas (V2.0) is intended for use as a reference standard for macaque neuroanatomical, functional, and connectional imaging studies, involving both cortical and subcortical targets. The SC21 and D99 digital templates are available as volumes and surfaces in standard NIFTI and GIFTI formats.

Connectome 2.0: Developing the next-generation ultra-high gradient strength human MRI scanner for bridging studies of the micro-, meso- and macro-connectome.

The first phase of the Human Connectome Project pioneered advances in MRI technology for mapping the macroscopic structural connections of the living human brain through the engineering of a whole-body human MRI scanner equipped with maximum gradient strength of 300 mT/m, the highest ever achieved for human imaging. While this instrument has made important contributions to the understanding of macroscale connectional topology, it has also demonstrated the potential of dedicated high-gradient performance scanners to provide unparalleled in vivo assessment of neural tissue microstructure. Building on the initial groundwork laid by the original Connectome scanner, we have now embarked on an international, multi-site effort to build the next-generation human 3T Connectome scanner (Connectome 2.0) optimized for the study of neural tissue microstructure and connectional anatomy across multiple length scales. In order to maximize the resolution of this in vivo microscope for studies of the living human brain, we will push the diffusion resolution limit to unprecedented levels by (1) nearly doubling the current maximum gradient strength from 300 mT/m to 500 mT/m and tripling the maximum slew rate from 200 T/m/s to 600 T/m/s through the design of a one-of-a-kind head gradient coil optimized to minimize peripheral nerve stimulation; (2) developing high-sensitivity multi-channel radiofrequency receive coils for in vivo and ex vivo human brain imaging; (3) incorporating dynamic field monitoring to minimize image distortions and artifacts; (4) developing new pulse sequences to integrate the strongest diffusion encoding and highest spatial resolution ever achieved in the living human brain; and (5) calibrating the measurements obtained from this next-generation instrument through systematic validation of diffusion microstructural metrics in high-fidelity phantoms and ex vivo brain tissue at progressively finer scales with accompanying diffusion simulations in histology-based micro-geometries. We envision creating the ultimate diffusion MRI instrument capable of capturing the complex multi-scale organization of the living human brain - from the microscopic scale needed to probe cellular geometry, heterogeneity and plasticity, to the mesoscopic scale for quantifying the distinctions in cortical structure and connectivity that define cyto- and myeloarchitectonic boundaries, to improvements in estimates of macroscopic connectivity.

Whole-Brain Imaging of Subvoxel T1-Diffusion Correlation Spectra in Human Subjects.

T1 relaxation and water mobility generate eloquent MRI tissue contrasts with great diagnostic value in many neuroradiological applications. However, conventional methods do not adequately quantify the microscopic heterogeneity of these important biophysical properties within a voxel, and therefore have limited biological specificity. We describe a new correlation spectroscopic (CS) MRI method for measuring how T1 and mean diffusivity (MD) co-vary in microscopic tissue environments. We develop a clinical pulse sequence that combines inversion recovery (IR) with single-shot isotropic diffusion encoding (IDE) to efficiently acquire whole-brain MRIs with a wide range of joint T1-MD weightings. Unlike conventional diffusion encoding, the IDE preparation ensures that all subvoxel water pools are weighted by their MDs regardless of the sizes, shapes, and orientations of their corresponding microscopic diffusion tensors. Accordingly, IR-IDE measurements are well-suited for model-free, quantitative spectroscopic analysis of microscopic water pools. Using numerical simulations, phantom experiments, and data from healthy volunteers we demonstrate how IR-IDE MRIs can be processed to reconstruct maps of two-dimensional joint probability density functions, i.e., correlation spectra, of subvoxel T1-MD values. In vivo T1-MD spectra show distinct cerebrospinal fluid and parenchymal tissue components specific to white matter, cortical gray matter, basal ganglia, and myelinated fiber pathways, suggesting the potential for improved biological specificity. The one-dimensional marginal distributions derived from the T1-MD correlation spectra agree well with results from other relaxation spectroscopic and quantitative MRI studies, validating the T1-MD contrast encoding and the spectral reconstruction. Mapping subvoxel T1-diffusion correlations in patient populations may provide a more nuanced, comprehensive, sensitive, and specific neuroradiological assessment of the non-specific changes seen on fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted MRIs (DWIs) in cancer, ischemic stroke, or brain injury.

Our Definition of Propeller Flaps and Their Classification.

The term propeller flap was introduced for the first time by Hyakusoku to define an island flap, based on a subcutaneous pedicle hub, that was rotated 90 degrees to correct scar contractures due to burns. With the popularization of perforator flaps, the propeller movement was applied for the first time to a skin island vascularized only by an isolated perforator, and the terms propeller and perforator flap were used together. Thereafter, the surgical technique of propeller flaps evolved and new applications developed. With the "Tokyo consensus," we proposed a definition and a classification schema for propeller flaps. A propeller flap was defined as an "island flap that reaches the recipient site through an axial rotation." The classification included the SPP (SPP) flap, the perforator pedicled propeller (PPP) flap, and the supercharged PPP (SCP) flap. A recent update added a new category, the axial pedicled propeller (APP) flap. Here we propose our updated and comprehensive classification of propeller flaps, taking into account the previous classification and subsequent publications. Based on their vascular pedicle, we consider the following five types of propellers: (1) SPP flap, 2.PPP flap, its subtype (2a) SCP flap, (3) APP flap, (4) muscle propeller flap, and (5) chimeric propeller flap. The variables that can be taken into account in the classification are as follows: type of nourishing pedicle, degrees of skin island rotation, position of the nourishing pedicle, artery of origin of the pedicle, and flap shape.

Measuring latency distribution of transcallosal fibers using transcranial magnetic stimulation.

BACKGROUND: Neuroimaging technology is being developed to enable non-invasive mapping of the latency distribution of cortical projection pathways in white matter, and correlative clinical neurophysiological techniques would be valuable for mutual verification. Interhemispheric interaction through the corpus callosum can be measured with interhemispheric facilitation and inhibition using transcranial magnetic stimulation. OBJECTIVE: To develop a method for determining the latency distribution of the transcallosal fibers with transcranial magnetic stimulation. METHODS: We measured the precise time courses of interhemispheric facilitation and inhibition with a conditioning-test paired-pulse magnetic stimulation paradigm. The conditioning stimulus was applied to the right primary motor cortex and the test stimulus was applied to the left primary motor cortex. The interstimulus interval was set at 0.1 ms resolution. The proportions of transcallosal fibers with different conduction velocities were calculated by measuring the changes in magnitudes of interhemispheric facilitation and inhibition with interstimulus interval. RESULTS: Both interhemispheric facilitation and inhibition increased with increment in interstimulus interval. The magnitude of interhemispheric facilitation was correlated with that of interhemispheric inhibition. The latency distribution of transcallosal fibers measured with interhemispheric facilitation was also correlated with that measured with interhemispheric inhibition. CONCLUSIONS: The data can be interpreted as latency distribution of transcallosal fibers. Interhemispheric interaction measured with transcranial magnetic stimulation is a promising technique to determine the latency distribution of the transcallosal fibers. Similar techniques could be developed for other cortical pathways.

Measuring conduction velocity distributions in peripheral nerves using neurophysiological techniques.

OBJECTIVE: To determine how long it takes for neural impulses to travel along peripheral nerve fibers in living humans. METHODS: A collision test was performed to measure the conduction velocity distribution of the ulnar nerve. Two stimuli at the distal and proximal sites were used to produce the collision. Compound muscle or nerve action potentials were recorded to perform the measurements on the motor or mixed nerve, respectively. Interstimulus interval was set at 1-5 ms. A quadri-pulse technique was used to measure the refractory period and calibrate the conduction time. RESULTS: Compound muscle action potential produced by the proximal stimulation started to emerge at the interstimulus interval of about 1.5 ms and increased with the increment in interstimulus interval. Two groups of motor nerve fibers with different conduction velocities were identified. The mixed nerve showed a wider conduction velocity distribution with identification of more subgroups of nerve fibers than the motor nerve. CONCLUSIONS: The conduction velocity distributions in high resolution on a peripheral motor and mixed nerve are different and this can be measured with the collision test. SIGNIFICANCE: We provided ground truth data to verify the neuroimaging pipelines for the measurements of latency connectome in the peripheral nervous system.

Composite rib and serratus anterior pedicle transfer for reconstruction of an osteomyelitis of the humerus.

We report the case of a 40 year-old male with Staphylococcus aureus osteomyelitis of the proximal humerus after open reduction and internal fixation of a fracture from motor vehicle accident. Removal of the osteosynthesis, extensive debridement and intravenous antibiotics administration was done followed by external fixation stabilization and reconstruction with a combined pedicled flap using the serratus anterior reversed flap and the 6th rib. At the last follow-up, healing of the bone flap was observed; the patient experienced useful motion of his upper extremity without any evidence of recurrent infection.