Publications by authors named "Mark Does"

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts.

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Alterations in white matter (WM) microstructure of the central nervous system have been shown to be pathophysiological presentations of various neurodegenerative disorders. Current methods for measuring such WM features require ex vivo tissue samples analyzed using electron microscopy. Magnetic Resonance Imaging (MRI) diffusion-weighted pulse sequences provide a non-invasive tool for estimating such microstructural features in vivo.

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Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I) were recently identified in mature OLG and shown to play a role in regulating myelin length.

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Purpose Of Review: This review summarizes recent advances in the assessment of bone quality using non-X-ray techniques.

Recent Findings: Quantitative ultrasound (QUS) provides multiple measurements of bone characteristics based on the propagation of sound through bone, the attenuation of that sound, and different processing techniques. QUS parameters and model predictions based on backscattered signals can discriminate non-fracture from fracture cases with accuracy comparable to standard bone mineral density (BMD).

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Biophysical diffusion-weighted imaging (DWI) models are increasingly used in neuroscience to estimate the axonal water fraction ( ), which in turn is key for noninvasive estimation of the axonal volume fraction ( ). These models require thorough validation by comparison with a reference method, for example, electron microscopy (EM). While EM studies often neglect the unmyelinated axons and solely report the fraction of myelinated axons, in DWI both myelinated and unmyelinated axons contribute to the DWI signal.

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The current clinical assessment of fracture risk lacks information about the inherent quality of a person's bone tissue. Working toward an imaging-based approach to quantify both a bone tissue quality marker (tissue hydration as water bound to the matrix) and a bone microstructure marker (porosity as water in pores), we hypothesized that the concentrations of bound water (C) are lower and concentrations of pore water (C) are higher in patients with osteoporosis (OP) than in age- and sex-matched adults without the disease. Using recent developments in ultrashort echo time (UTE) magnetic resonance imaging (MRI), maps of C and C were acquired from the uninjured distal third radius (Study 1) of 20 patients who experienced a fragility fracture of the distal radius (Fx) and 20 healthy controls (Non-Fx) and from the tibia mid-diaphysis (Study 2) of 30 women with clinical OP (low T-scores) and 15 women without OP (normal T-scores).

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Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues.

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Purpose: MR microscopy is in principle capable of producing images at cellular resolution (<10 µm), but various factors limit the quality achieved in practice. A recognized limit on the signal to noise ratio and spatial resolution is the dephasing of transverse magnetization caused by diffusion of spins in strong gradients. Such effects may be reduced by using phase encoding instead of frequency encoding read-out gradients.

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MRI measures of bound and/or pore water concentration in cortical bone offer potential diagnostics of bone fracture risk. The transverse relaxation characteristics of both bound and pore water are relatively well understood and have been used to design clinical MRI pulse sequences to image each water pool quantitatively. However, these methods are also sensitive to longitudinal relaxation characteristics, which have been less well studied.

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Purpose: Extend fast, two-dimensional (2D) methods of bound and pore water mapping in bone to arbitrary slice orientation.

Methods: To correct for slice profile artifacts caused by gradient errors of half pulse 2D ultra-short echo time (UTE), we developed a library of predistorted gradient waveforms that can be used to interpolate optimized gradient waveforms for 2D UTE slice selection. We also developed a method to estimate and correct for a bulk phase difference between the two half pulse excitations used for 2D UTE signal excitation.

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FOXG1 Syndrome (FS) is a devastating neurodevelopmental disorder that is caused by a heterozygous loss-of-function (LOF) mutation of the FOXG1 gene, which encodes a transcriptional regulator important for telencephalic brain development. People with FS have marked developmental delays, impaired ambulation, movement disorders, seizures, and behavior abnormalities including autistic features. Current therapeutic approaches are entirely symptomatic, however the ability to rescue phenotypes in mouse models of other genetic neurodevelopmental disorders such as Rett syndrome, Angelman syndrome, and Phelan-McDermid syndrome by postnatal expression of gene products has led to hope that similar approaches could help modify the disease course in other neurodevelopmental disorders such as FS.

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Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) enables the noninvasive treatment of the deep brain. This capacity relies on the ability to focus acoustic energy through the in-tact skull, a feat that requires accurate estimates of the acoustic velocity in individual patient skulls. In current practice, these estimates are generated using a pretreatment computed tomography (CT) scan and then registered to a magnetic resonance (MR) dataset on the day of the treatment.

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Ultrashort echo time (UTE) MRI techniques can be used to image the concentration of water in bones. Particularly, quantitative MRI imaging of collagen-bound water concentration () and pore water concentration () in cortical bone have been shown as potential biomarkers for bone fracture risk. To investigate the effect of and on the evaluation of bone mechanical properties, MRI-based finite element models of cadaver radii were generated with tissue material properties derived from 3 D maps of and measurements.

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Purpose: RACETE (refocused acquisition of chemical exchange transferred excitations) is a recently developed approach to imaging solute exchange with water. However, it lacks biophysical specificity, as it is sensitive to exchange rates, relaxation rates, solute concentration, and macromolecular content. We modified this sequence and developed a protocol and corresponding metric with specific sensitivity to the solute exchange rate and hence a means for mapping pH.

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High resolution, peripheral quantitative computed tomography (HR-pQCT) scanners can now characterize an individual's trabecular architecture, cortical structure, and volumetric bone mineral density at a nominal resolution of 61 μm. While predictions of failure load of the distal radius and tibial diaphysis in compression by finite element analysis (FEA) of HR-pQCT scans have been validated against mechanical tests of cadaveric bones in compression, namely for images with nominal resolutions of 82 μm and 165 μm, the HR-pQCT parameters that best predict bending strength of cortical bone remain unknown. Therefore, we scanned cadaveric forearms from 31 elderly donors (Female: 72.

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Chemical exchange saturation transfer (CEST) methods measure the effect of magnetization exchange between solutes and water. While CEST methods are often implemented using a train of off-resonant shaped RF pulses, they are typically analyzed as if the irradiation were continuous. This approximation does not account for exchange of rotated magnetization, unique to pulsed irradiation and exploited by chemical exchange rotation transfer methods.

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Objective: Primary repair of peripheral nerves is recommended following transection; however, patient management following repair is challenged by a lack of biomarkers to nerve regeneration. Previous studies have demonstrated that diffusion magnetic resonance imaging (MRI) may provide viable biomarkers of nerve regeneration in injury models; though, these methods have not been systematically evaluated in graded partial transections and repairs.

Methods: Ex vivo diffusion MRI was performed in fixed rat sciatic nerve samples 4 or 12 weeks following partial nerve transection and repair (25% cut = 12, 50% cut = 12 and 75% cut = 11), crush injuries (n = 12), and sham surgeries (n = 9).

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The broad snouted caiman is a crocodylian native to South America that is subject to extensive conservation management in both wild and farming environments. Although reproductive behaviors like egg laying and clutch care have been examined in this species, little else is known about their copulatory system. We examined the anatomy of male and female cloacal and genital tissues ex vivo to build hypotheses of their interactions during copulation and the effects of that interaction on insemination.

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Accurate measurement of gradient waveform errors can often improve image quality in sequences with time varying readout and excitation waveforms. Self-encoding or offset-slice sequences are commonly used to measure gradient waveforms. However, the self-encoding method requires a long scan time, while the offset-slice method is often low precision, requiring the thickness of the excited slice to be small compared to the maximal k-space encoded by the test waveform.

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The metabotropic glutamate receptor 7 (mGlu7) is a G protein-coupled receptor that has been recently linked to neurodevelopmental disorders. This association is supported by the identification of GRM7 variants in patients with autism spectrum disorder, attention deficit hyperactivity disorder, and severe developmental delay. One GRM7 mutation previously reported in 2 patients results in a single amino acid change, I154T, within the mGlu7 ligand-binding domain.

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Objective: Management of peripheral nerve injuries requires physicians to rely on qualitative measures from patient history, electromyography, and physical exam. Determining a successful nerve repair can take months to years for proximal injuries, and the resulting delays in clinical decision-making can lead to a negative impact on patient outcomes. Early identification of a failed nerve repair could prevent permanent muscle atrophy and loss of function.

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Noninvasive estimation of mean axon diameter presents a new opportunity to explore white matter plasticity, development, and pathology. Several diffusion-weighted MRI (DW-MRI) methods have been proposed to measure the average axon diameter in white matter, but they typically require many diffusion encoding measurements and complicated mathematical models to fit the signal to multiple tissue compartments, including intra- and extra-axonal spaces. Here, Monte Carlo simulations uncovered a straightforward DW-MRI metric of axon diameter: the change in radial apparent diffusion coefficient estimated at different effective diffusion times, ΔD.

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In chemical exchange saturation transfer (CEST) imaging, the signal at 2.6 ppm from the water resonance in muscle has been assigned to phosphocreatine (PCr). However, this signal has limited specificity for PCr since the signal is also sensitive to exchange with protein and macromolecular protons when using some conventional quantification methods, and will vary with changes in the water longitudinal relaxation rate.

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The phallic glans of the American alligator (Alligator mississippiensis) is the distal termination of the semen-conducting sulcus spermaticus and during copulation has the closest, most intimate mechanical interactions with the female urodeum, the middle cloacal chamber that contains the opening to the vaginal passages and oviducts. However, the details of this interface leading to insemination and gamete uptake are unclear. Here, we: (1) histologically characterize the underlying tissue types and morphologically quantify the shape changes associated with glans inflation into the copulatory conformation, (2) digitally reconstruct from MRI the 3D shape of functional tissue compartments, and (3) diffusible iodine-based contrast-enhanced computed tomography image the copulatory fit between male phallus and female cloaca.

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