Biology subjects

Martin, B. A.

Publications and source records attributed to Martin, B. A..

5 recordsLinked to original sources

bioRxiv2026

Simultaneous Real-time Imaging of Neurofluid and Neurovascular Dynamics Using Ultrafast Flow-weighted Echo-Planar Imaging

Cerebrospinal fluid (CSF) circulation is tightly coupled to cerebral blood flow under the fixed-volume constraint of the cranial vault, with cardiac pulsations and respiration acting as dominant physiological drivers. Disruption of these flow dynamics has been implicated in various neurological disorders, motivating the need for imaging methods that capture CSF and vascular flow simultaneously and in real time. Conventional phase contrast MRI (PC-MRI) provides quantitative CSF velocity measurements but relies on cardiac gating and velocity encoding, which limit temporal resolution, dynamic range, and sensitivity to non-cardiac fluctuations. Here, we introduce self-gated ultrafast real-time flow-weighted echo-planar imaging (SURF-EPI), an inflow-weighted approach in which signal intensity reflects the replacement of saturated spins by freshly inflowing, unsaturated water molecules, yielding higher signal with higher flow. This allows simultaneous assessment of arterial inflow, venous outflow, and CSF motion at high temporal resolution. SURF-EPI was acquired at the C2-C3 spinal level, enabling real-time imaging of CSF flow dynamics in the cervical spinal canal alongside arterial and venous blood flow in major cervical vessels (frame-rate: 21.7 Hz). In addition to frequency-domain analyses, we leveraged intrinsic arterial signal fluctuations as a timing reference to reconstruct cardiac-resolved CSF dynamics for individual cardiac cycles without external physiological recordings. Frequency-domain analysis revealed distinct spectral signatures in CSF flow compared with neurovascular flow, including broadened cardiac peaks and enhanced respiratory modulation, particularly within the ventral spinal canal. In contrast, dorsal CSF showed increased power within the cardiac frequency band, higher coherence with cervical vasculature at the cardiac frequency, and reduced non-cardiac contributions. Time-domain analysis showed strong correlation between CSF flow waveforms derived from SURF-EPI and PC-MRI. Beyond ensemble-averaged waveforms, SURF-EPI enabled beat-to-beat analysis, revealing substantial cycle-to-cycle variability in CSF flow that is not captured by time-averaged gated approaches. Together, these findings establish SURF-EPI as a rapid, complementary framework to PC-MRI, enabling real-time neurofluid imaging with integrated time- and frequency-domain characterization of CSF and neurovascular flow dynamics.

neuroscience↗

bioRxiv2023

Flavinated SDHA Underlies the Change in Intrinsic Optical Properties of Oral Cancers

The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lie at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination. Autofluorescence from a 70 kDa flavoprotein, succinate dehydrogenase A (SDHA), was found to be responsible for changes in optical properties within the FAD spectral region with lower levels of flavinated SDHA in OSCC cells. Since flavinated SDHA is required for functional complexation with succinate dehydrogenase B (SDHB), decreased SDHB levels were observed in human OSCC tissue relative to normal tissues. Accordingly, the metabolism of OSCC cells was found to be significantly altered relative to normal cells, revealing vulnerabilities for both diagnosis and targeted therapy. Optimizing non-invasive tools based on optical and metabolic signatures of cancers will enable more precise and early diagnosis leading to improved outcomes in patients.

cancer biology↗

bioRxiv2020

Additional analyses exploring the hypothesized transdifferentiation of plasmablasts to developing neutrophils in severe COVID-19

We thank Alquicira-Hernandez et al. for their reanalysis of our single-cell transcriptomic dataset profiling peripheral immune responses to severe COVID-19. We agree that careful analysis of single-cell sequencing data is important for generating cogent hypotheses but find several aspects of their criticism of our analysis to be problematic. Here we respond briefly to misunderstandings and inaccuracies in their commentary that may have led to misinformed interpretation of our results.

immunology↗

bioRxiv2020

Intrathecal catheter implantation decreases cerebrospinal fluid dynamics in cynomolgus monkeys

A detailed understanding of the CSF dynamics is essential for testing and evaluation of intrathecal drug delivery. Preclinical work using large-animal models (e.g., monkeys, dogs and sheep) has great utility for defining spinal drug distribution/pharmacokinetics and provide an important tool for defining safety. In this study, we investigated the impact of catheter implantation in the sub-dural space on CSF flow dynamics in Cynomolgus monkeys. Magnetic resonance imaging (MRI) was performed before and after catheter implantation to quantify the differences based on catheter placement location in the cervical compared to the lumbar spine. Several geometric and hydrodynamic parameters were calculated based on the 3D segmentation and flow analysis. Hagen-Poiseuille equation was used to investigate the impact of catheter implantation on flow reduction and hydraulic resistance. A linear mixed-effects model was used in this study to investigate if there is a statistically significant difference between cervical and lumbar implantation, or between two MRI time points. Results showed that geometric parameters did not change statistically across MRI measurement time points and did not depend on catheter location. However, catheter insertion did have a significant impact on the hydrodynamic parameters and the effect was greater with the cervical implantation. CSF flow rate decreased up to 54.7% when the catheter located in the cervical region. The maximum flow rate reduction in the lumbar implantation group was 21%. Overall, lumbar catheter implantation disrupted CSF dynamics to a lesser degree than cervical catheter implantation and this effect remained up to two weeks post-catheter implantation

pharmacology and toxicology↗

bioRxiv2020

Design of optical imaging probes by screening of diverse substrate libraries directly in disease tissue extracts

Fluorescently-quenched probes that are specifically activated in the cancer microenvironment have great potential application for diagnosis, early detection and surgical guidance. These probes are often designed to target specific enzymes associated with disease by direct optimization using single purified targets. However, this can result in painstaking chemistry efforts to produce a probe with suboptimal performance when applied in vivo. We describe here an alternate, unbiased activity-profiling approach in which whole tissue extracts are used to directly identify optimal peptide sequences for probe design. Screening of mouse mammary tumor extracts with a hybrid combinatorial substrate library (HyCoSuL) identified a combination of natural and non-natural amino acid residues that could be used to generate highly efficient tumor-specific fluorescently quenched substrate probes. The most effective probe is significantly brighter than any of our previously reported tumor imaging probes designed for specific proteases and robustly discriminates tumor tissue from adjacent healthy tissue in a mouse model of cancer. Importantly, although the probes were developed by screening mouse mammary tumor tissues, they are able to effectively distinguish human ductal carcinomas from normal breast tissue with similar reactivity profiles to those observed in mouse tissues. This new strategy simplifies and enhances the process of probe optimization by direct screening in a tissue of interest without any a priori knowledge of enzyme targets. It has the potential to be applied to advance the development of probes for diverse disease states for which clinical or animal model tissues are available.

bioengineering↗