Can MRI Be Used as a Sensor to Record Neural Activity?

Magnetic resonance provides exquisite anatomical images and functional MRI monitors physiological activity by recording blood oxygenation. This review attempts to answer the following question: Can MRI be used as a sensor to directly record neural behavior? It considers MRI sensing of electrical activity in the heart and in peripheral nerves before turning to the central topic: recording of brain activity. The primary hypothesis is that bioelectric current produced by a nerve or muscle creates a magnetic field that influences the magnetic resonance signal, although other mechanisms for detection are also considered. Recent studies have provided evidence that using MRI to sense neural activity is possible under ideal conditions. Whether it can be used routinely to provide functional information about brain processes in people remains an open question. The review concludes with a survey of artificial intelligence techniques that have been applied to functional MRI and may be appropriate for MRI sensing of neural activity.

Biomagnetism: The First Sixty Years.

Biomagnetism is the measurement of the weak magnetic fields produced by nerves and muscle. The magnetic field of the heart-the magnetocardiogram (MCG)-is the largest biomagnetic signal generated by the body and was the first measured. Magnetic fields have been detected from isolated tissue, such as a peripheral nerve or cardiac muscle, and these studies have provided insights into the fundamental properties of biomagnetism. The magnetic field of the brain-the magnetoencephalogram (MEG)-has generated much interest and has potential clinical applications to epilepsy, migraine, and psychiatric disorders. The biomagnetic inverse problem, calculating the electrical sources inside the brain from magnetic field recordings made outside the head, is difficult, but several techniques have been introduced to solve it. Traditionally, biomagnetic fields are recorded using superconducting quantum interference device (SQUID) magnetometers, but recently, new sensors have been developed that allow magnetic measurements without the cryogenic technology required for SQUIDs.

Sperm DNA fragmentation testing in clinical management of reproductive medicine.

Background: Approximately 8%-12% of couples worldwide face infertility, with infertility of individuals assigned male at birth (AMAB) contributing to at least 50% of cases. Conventional semen analysis commonly used to detect sperm abnormalities is insufficient, as 30% of AMAB patients experiencing infertility show normal results in this test. From a genetic perspective, the assessment of sperm DNA fragmentation (SDF) is important as a parameter of sperm quality. Methods: In this narrative study, we review and discuss pathophysiological causes, DNA repair mechanisms, and management of high SDF. We then summarize literature exploring the association between SDF and reproductive outcomes. Main Findings: Recent systematic reviews and meta-analyses have revealed a significant association between high SDF in AMAB individuals and adverse reproductive outcomes including embryo development, natural conception, intrauterine insemination, and in vitro fertilization. However, the association with live birth rates and pregnancy rates following intracytoplasmic injection remains inconclusive. The disparities among quantitative assays, inconsistent reference range values, absent high-quality prospective clinical trials, and clinical heterogeneity in AMAB patients with elevated SDF represent the main limitations affecting SDF testing. Conclusion: The evaluation and management of SDF plays an important role in a subset of AMAB infertility, but widespread integration into clinical guidelines will require future high-quality clinical trials and assay standardization.

The mechanical bidomain model of cardiac muscle with curving fibers.

In the heart, cardiac muscle fibers curve creating zones of membrane forces resulting in regions of mechanotransduction. This study uses the finite difference method to solve the mechanical bidomain equations numerically for a complex fiber geometry. The magnitude of the active tension T is constant but its direction makes an angle with the x-axis that varies with position. Differences between the intracellular and extracellular displacements result from the bidomain behavior of the tissue that gives rise to forces on the integrin proteins in the membrane. The long-term goal is to use the mechanical bidomain model to suggest experiments and make predictions about growth and remodeling in the heart.

Heterogeneous anisotropic magnetic susceptibility of the myelin-water layers causes local magnetic field perturbations in axons.

One goal of MRI is to determine the myelin water fraction in neural tissue. One approach is to measure the reduction in T2 * arising from microscopic perturbations in the magnetic field caused by heterogeneities in the magnetic susceptibility of myelin. In this paper, analytic expressions for the induced magnetic field distribution are derived within and around an axon, assuming that the myelin susceptibility is anisotropic. Previous models considered the susceptibility to be piecewise continuous, whereas this model considers a sinusoidally varying susceptibility. Many conclusions are common in both models. When the magnetic field is applied perpendicular to the axon, the magnetic field in the intraaxonal space is uniformly perturbed, the magnetic field in the myelin sheath oscillates between the lipid and water layers, and the magnetic field in the extracellular space just outside the myelin sheath is heterogeneous. These field heterogeneities cause the spins to dephase, shortening T2 *. When the magnetic field is applied along the axon, the field is homogeneous within water-filled regions, including between lipid layers. Therefore the spins do not dephase and the magnetic susceptibility has no effect on T2 *. Generally, the response of an axon is given as the superposition of these two contributions. The sinusoidal model uses a different set of approximations compared with the piecewise model, so their common predictions indicate that the models are not too sensitive to the details of the myelin-water distribution. Other predictions, such as the sensitivity to water diffusion between myelin and water layers, may highlight differences between the two approaches. Copyright © 2016 John Wiley & Sons, Ltd.

Modeling bipolar stimulation of cardiac tissue.

Unipolar stimulation of cardiac tissue is often used in the design of cardiac pacemakers because of the low current required to depolarize the surrounding tissue at rest. However, the advantages of unipolar over bipolar stimulation are not obvious at shorter coupling intervals when the tissue near the pacing electrode is relatively refractory. Therefore, this paper analyzes bipolar stimulation of cardiac tissue. The strength-interval relationship for bipolar stimulation is calculated using the bidomain model and a recently developed parsimonious ionic current model. The strength-interval curves obtained using different electrode separations and arrangements (electrodes placed parallel to the fibers versus perpendicular to the fibers) indicate that bipolar stimulation results in more complex activation patterns compared to unipolar stimulation. An unusually low threshold stimulus current is observed when the electrodes are close to each other (a separation of 1 mm) because of break excitation. Unlike for unipolar stimulation, anode make excitation is not present during bipolar stimulation, and an abrupt switch from anode break to cathode make excitation can cause dramatic changes in threshold with very small changes in the interval. These results could impact the design of implantable pacemakers and defibrillators.

The Mechanism of Reflection Type Reentry: A Simulation Study.

INTRODUCTION: Reflection is a special type of reentry in which an electrical wave front travels in a forward direction through tissue that is then re-excited by a wave front that propagates backward. This type of reentry has been studied computationally in 1-dimensional fibers and verified experimentally. Different hypotheses explaining reflected reentry have been proposed based on the structure and heterogeneity of the tissue properties, but the mechanism remains uncertain. METHODS AND RESULTS: We used the bidomain model to represent cardiac tissue and the Luo-Rudy model to describe the active membrane properties. We consider an ischemic region in a volume of ventricular myocardium. Our results show that a slow depolarization in the ischemic border zone caused by electrotonic coupling to depolarized tissue in the normal region creates a delay between proximal and distal regions that produces enough electrotonic current in the distal region to re-excite the proximal region. CONCLUSION: Our simulation shows that an early afterdepolarization (EAD) is not the source of the reflection. It depends on the pacing interval and stimulus strength necessary to maintain enough time delay between proximal and distal regions.

Intracellular calcium and the mechanism of the dip in the anodal strength-interval curve in cardiac tissue.

BACKGROUND: The strength-interval (SI) curve is an important measure of refractoriness in cardiac tissue. The anodal SI curve contains a "dip" in which the S2 threshold increases with interval. Two explanations exist for this dip: (1) electrotonic interaction between regions of depolarization and hyperpolarization; and (2) the sodium-calcium exchange (NCX) current. The goal of this study is to use mathematical modeling to determine which explanation is correct. METHODS AND RESULTS: The bidomain model represents cardiac tissue and the Luo-Rudy model describes the active membrane. The SI curve is determined by applying a threshold stimulus at different time intervals after a previous action potential. During space-clamped and equal-anisotropy-ratios simulations, anodal excitation does not occur. During unequal-anisotropy-ratios simulations, electrotonic currents, not membrane currents, are present during the few milliseconds before excitation. The dip disappears with no NCX current, but is present with 50% or 75% reduction of it. The calcium-induced-calcium-release (CICR) current has little effect on the dip. CONCLUSIONS: These results indicate that neither the NCX nor the CICR current is responsible for the dip in the anodal SI curve. It is caused by the electrotonic interaction between regions of depolarization and hyperpolarization following the S2 stimulus.

The magnetocardiogram.

The magnetic field produced by the heart's electrical activity is called the magnetocardiogram (MCG). The first 20 years of MCG research established most of the concepts, instrumentation, and computational algorithms in the field. Additional insights into fundamental mechanisms of biomagnetism were gained by studying isolated hearts or even isolated pieces of cardiac tissue. Much effort has gone into calculating the MCG using computer models, including solving the inverse problem of deducing the bioelectric sources from biomagnetic measurements. Recently, most magnetocardiographic research has focused on clinical applications, driven in part by new technologies to measure weak biomagnetic fields.

Depth-Dependent Strain Model (1D) for Anisotropic Fibrils in Articular Cartilage.

The mechanical response of articular cartilage (AC) under compression is anisotropic and depth-dependent. AC is osmotically active, and its intrinsic osmotic swelling pressure is balanced by its collagen fibril network. This mechanism requires the collagen fibers to be under a state of tensile pre-strain. A simple mathematical model is used to explain the depth-dependent strain calculations observed in articular cartilage under 1D axial compression (perpendicular to the articular surface). The collagen fibers are under pre-strain, influenced by proteoglycan concentration (fixed charged density, FCD) and collagen stiffness against swelling stress. The stiffness is introduced in our model as an anisotropic modulus that varies with fibril orientation through tissue depth. The collagen fibers are stiffer to stretching parallel to their length than perpendicular to it; when combined with depth-varying FCD, the model successfully predicts how tissue strains decrease with depth during compression. In summary, this model highlights that the mechanical properties of cartilage depend not only on proteoglycan concentration but also on the intrinsic properties of the pre-strained collagen network. These properties are essential for the proper functioning of articular cartilage.

Associations Between Sodium-Glucose Co-transporter 2 Inhibitors and Urologic Diseases: Implications for Lower Urinary Tract Symptoms From a Multi-State Health System Analysis.

OBJECTIVE: To analyze the frequency of new urologic visits and urologic diagnoses in patients prescribed sodium-glucose co-transporter-2 inhibitors (SGLT-2is). MATERIAL AND METHODS: Records from a multi-state health system between 2014 and 2022 were reviewed to identify patients referred for outpatient urology evaluation within 2 years of diabetes medication prescription. Patients were stratified by the prescription of SGLT-2is or another diabetes medication. Frequency of urology visits within 1-year, urologic diagnoses, and prescriptions to treat lower urinary tract symptoms (LUTS) were compared. Patients were stratified by whether they had achieved HbA1c goal (≥7% or <7%) following treatment as well as by sex. Multivariable logistic regression was performed to determine if SGLT-2 use independently predicted outcomes of interest. RESULTS: 163,827 patients met inclusion criteria. Use of SGLT-2is was associated with a higher frequency of early urologic referral, balanitis/balanoposthitis, overactive bladder, urinary frequency, urgency, and need for LUTS medications in males with HbA1c ≥7%. Females on SGLT-2is with HbA1c ≥7% also had higher rates of urinary incontinence. In those with HbA1c <7%, only balanitis/balanoposthitis and urinary incontinence were higher in the SGLT-2i cohorts for males and females, respectively. Multivariable analysis found SGLT-2i use as predictive of early urology referral, balanitis/balanoposthitis, urinary urgency, frequency, overactive bladder, and need for LUTS medications in males. Multivariable analysis of females demonstrated similar results. CONCLUSION: SGLT-2is may lead to worse urologic outcomes and increased utilization of urologic care relative to other diabetic medications. Future studies are necessary to identify which patients are at highest risk of adverse urologic outcomes.

The relationship between hematologic malignancies on male hypogonadism: a scoping review.

INTRODUCTION: The associated symptoms of hypogonadism have been reported in patients with various types of cancer. However, the prevalence and significance of hypogonadism among certain hematologic malignancies have not been completely summarized in recent literature. OBJECTIVE: In this review we aimed to examine the current literature on hypogonadism in patients with hematologic malignancies, with emphasis on leukemias, lymphomas, and multiple myeloma (MM). METHODS: This review included relevant studies published before July 2023 that were retrieved through a search of PubMed using the keywords "hematologic cancer," "hematologic malignancy," blood cancer," "leukemia," "lymphoma," "hypogonadism," "multiple myeloma," and "testosterone." RESULTS: The search yielded 214 studies, of which 21 met the inclusion criteria. Commonly reported findings were that patients who had received hematopoietic stem cell therapy for acute lymphoblastic leukemia and acute myelogenous leukemia as children had laboratory-confirmed hypogonadism as adults. However, the impact of these diseases on hypogonadal symptoms was variable in these studies.Studies reporting on lymphoma and hypogonadism had mixed results, with some studies finding that the degree of cytotoxic chemotherapy was associated with hypogonadism, while others showed no correlation. Regardless, multiple studies found that hypogonadism secondary to lymphoma treatment and symptoms of hypogonadism had no apparent association.The most comprehensive assessment of the frequency of hypogonadism in an MM cohort found that 74% of 561 MM patients were classified as hypogonadal compared to 33% of patients in a control population. Testosterone supplementation was found to lower interleukin-6 levels, which could potentially help manage some of the adverse effects of MM, including decreased bone mineral density. CONCLUSION: There is a relationship between hematologic malignancies and hypogonadism, which is likely multifactorial. In this review we established that the most plausible factors are related to the secondary effects of gonadotoxic treatments and/or systemic inflammatory responses to the diseases.

Utilization of Re-VASC, the Novel Retroperitoneal Neovascularity Scoring System, for Characterization of T1a Small Renal Masses.

Purpose: Early characterization of small (T1a, <4 cm) renal masses is imperative for patient care and treatment planning. Renal biopsy is a sensitive and specific procedure that can accurately differentiate small renal masses as malignant or benign. However, it is an invasive procedure with a nonnegligible complication rate and is not performed routinely at most institutions. In this study, we sought to apply the Retroperitoneal Vascularity Assessment and Scoring in Carcinoma (Re-VASC) scoring system to T1a renal masses and analyzed whether it could differentiate these masses as benign or malignant. Methods: We obtained Institutional Review Board approval to retrospectively examine the records of all patients who presented to our single, urban academic referral center for surgical treatment of renal cell carcinoma (RCC). For the malignant group, patients with a diagnosis of T1a RCC from pathologic evaluation were included. Additionally, patients with a histopathological diagnosis of a T1a nonmalignant renal mass (fat poor-angiomyolipoma or oncocytoma) were included in our benign group. Results: This study includes 57 benign and 69 malignant T1a renal tumors. Average size for benign and malignant masses were 2.47 and 2.63, respectively (p = 0.267). Analysis demonstrated no significant difference between both groups in terms of sex, laterality, or size. The average Re-VASC score of benign and malignant masses was 0.175 and malignant masses was 0.784, respectively (p < 0.001). Additionally, the Re-VASC score was independently associated with malignancy with an odds ratio of 2.223 (p = 0.0109). Conclusion: The Re-VASC scoring system exhibits significantly greater values for malignant T1a renal masses when compared to benign masses. As a result, it shows promise as an adjunctive tool to renal biopsy for clinical decision-making. Further assessment of Re-VASC's true efficacy as a diagnostic marker will include prospective evaluation of a larger multicenter population.

Transmembrane current imaging in the heart during pacing and fibrillation.

Recently, we described a method to quantify the time course of total transmembrane current (Im) and the relative role of its two components, a capacitive current (Ic) and a resistive current (Iion), corresponding to the cardiac action potential during stable propagation. That approach involved recording high-fidelity (200 kHz) transmembrane potential (Vm) signals with glass microelectrodes at one site using a spatiotemporal coordinate transformation via measured conduction velocity. Here we extend our method to compute these transmembrane currents during stable and unstable propagation from fluorescence signals of Vm at thousands of sites (3 kHz), thereby introducing transmembrane current imaging. In contrast to commonly used linear Laplacians of extracellular potential (Ve) to compute Im, we utilized nonlinear image processing to compute the required second spatial derivatives of Vm. We quantified the dynamic spatial patterns of current density of Im and Iion for both depolarization and repolarization during pacing (including nonplanar patterns) by calibrating data with the microelectrode signals. Compared to planar propagation, we found that the magnitude of Iion was significantly reduced at sites of wave collision during depolarization but not repolarization. Finally, we present uncalibrated dynamic patterns of Im during ventricular fibrillation and show that Im at singularity sites was monophasic and positive with a significant nonzero charge (Im integrated over 10 ms) in contrast with nonsingularity sites. Our approach should greatly enhance the understanding of the relative roles of functional (e.g., rate-dependent membrane dynamics and propagation patterns) and static spatial heterogeneities (e.g., spatial differences in tissue resistance) via recordings during normal and compromised propagation, including arrhythmias.

Boundary Layers and the Distribution of Membrane Forces Predicted by the Mechanical Bidomain Model.

The mechanical bidomain model is a mathematical description of the elastic properties of cardiac tissue. The unique feature of the bidomain model is that it is a macroscopic continuum representation of tissue that nevertheless accounts for the intracellular and extracellular spaces individually, thereby focusing on mechanical forces arising across the cell membrane. In this paper, the mechanical bidomain model describes a two-dimensional sheet of cardiac tissue undergoing a uniform active tension. At the boundary, the tissue sheet is free to move. Analytical solutions are found for the intracellular and extracellular displacements and pressures. The model predicts that membrane forces, which may be responsible for phenomena such as mechanotransduction and remodeling, are large near the tissue boundary, and fall off rapidly with distance from the boundary.

The Electric Field Induced by a Microcoil During Magnetic Stimulation.

OBJECTIVE: The purpose of this study is to calculate the electric field produced by an implanted microcoil during magnetic stimulation of the brain. METHODS: The electric field of a microcoil was calculated numerically. RESULTS: The maximum value of the induced electric field is approximately 0.000026 V/m for a 1 mA, 3 kHz current passed through the coil. CONCLUSION: This electric field value is too small to cause neural stimulation. SIGNIFICANCE: Previous studies reporting magnetic stimulation using a microcoil must have been exciting neurons by some other mechanism.

Revenue and Cost Analysis of a System Utilizing Natural Language Processing and a Nurse Coordinator for Radiology Follow-up Recommendations.

Radiology reports often contain recommendations for follow-up imaging, Provider adherence to these radiology recommendations can be incomplete, which may result in patient harm, lost revenue, or litigation. This study sought to perform a revenue assessment of a hybrid natural language processing (NLP) and human follow-up system. Reports generated from January 2020 to April 2021 that were indexed as overdue from follow-up recommendations by mPower Follow-Up Recommendation Algorithm (Nuance Communications Inc., Burlington, MA), were assessed for follow up and revenue. Follow-up exams completed because of the hybrid system were tabulated and given revenue amounts based on Medicare national reimbursement rates. These rates were then summated. A total of n =3011 patients were flagged via the mPower algorithm as having not received a timely follow-up indicated for procedure. Of these, n = 427 required the quality nurse to contact their healthcare provider to place orders. The follow-up imaging of these patients accounted for $62,937.66 of revenue. This revenue was calculated as higher than personnel cost (based on national average quality and safety nurse salary and time allotted on follow-ups). Our results indicate that a hybrid human-artificial intelligence follow-up system can be profitable, while potentially adding to patient safety. Our revenue figure likely significantly underestimates the true revenue obtained at our institution. This was due to the use of Medicare national reimbursement rates to calculate revenue, for the purposes of generalizability.

Novel Retroperitoneal Neovascularity Scoring System in Renal Cell Carcinoma Tumor Staging.

Purpose: Renal cell carcinoma (RCC) is the most common type of kidney cancer worldwide. Although radiologists assess enhancement patterns of renal tumors to predict tumor pathology report, to our knowledge, no formal scoring system has been created and validated to assess the level of neovascularity in RCC, despite its critical role in cancer metastases. In this study, we characterized and analyzed the level of angiogenesis in tumor-burdened kidneys and their benign counterparts. We then created and validated a scoring scale for neovascularity that can help predict tumor staging for RCC. Methods: After Institutional Review Board approval, the charts of patients who had undergone operation for RCC between January 13, 2014 and February 4, 2020 were retrospectively reviewed for inclusion in this study. Inclusion criteria were a diagnosis of RCC, simple/radical nephrectomy, preoperative contrast-enhanced CT scans, and complete pathology reports. Neovascularity was scored on a scale of 0-4 where 0 = no neovascularity detected, 1 = a single vessel <3 mm wide, 2 = a single vessel ≥3 mm wide, 3 = multiple vessels <3 mm wide, and 4 = multiple vessels ≥3 mm wide. Results: A total of 227 patients were included in this study. Most of the tumor pathology reports were clear cell carcinoma, regardless of tumor staging. The average neovascularity score was 1.07 for pT1x tumors, 2.83 for pT2x tumors, and 3.04 for pT3x tumors. There was a significant difference in neovascularity score between pT1x and pT2x tumors (p = 0.0046), pT1x and pT3x tumors (p < 0.0001), and benign kidneys and kidneys with RCC (p < 0.0001). Conclusion: Our novel vascular scoring system for RCC demonstrates significant correlation with RCC pathological tumor staging. This scoring system may be utilized as part of a comprehensive radiological assessment of renal tumors, potentially improving tumor characterization and clinical decision making.

Targeting Hypoxia-Inducible Factor-1α for the Management of Hepatocellular Carcinoma.

Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.