Biology subjects

Zhou, I. Y.

Publications and source records attributed to Zhou, I. Y..

3 recordsLinked to original sources

bioRxiv2026

A single-plane electrical impedance tomography framework for integrated liver and kidney assessment

Chronic liver and kidney diseases frequently coexist, but their assessment typically requires separate clinical workflows involving serum-based estimated glomerular filtration rate (eGFR) testing and liver elastography-based controlled attenuation parameter (CAP). Electrical impedance tomography (EIT) has recently shown promise for providing portable, non-invasive proxies for both reference measurements. However, existing multi-organ EIT assessment still requires different acquisition protocols for each organ. To simplify this procedure, we assessed the feasibility of a single-plane EIT framework for reconstructing organ-specific images and estimating liver and kidney health from one abdominal belt placement. Across diverse abdominal belt locations, opposite-plane deviation was significantly greater for eGFREIT estimates (2.92%; IQR, 0.46-12.53%) than for CAPEIT estimates (0.94%; IQR, 0.66-1.70%) (p < 0.01). For both organs, compared to images acquired at the conventional organ-specific planes, image correlation significantly decreased (both, p < 0.05) and normalized root mean squared error significantly increased (both, p < 0.05) at the furthest imaging plane, with these differences being numerically larger for the kidney. Together, these results supported the kidney plane as the preferred location for multi-organ assessment. Test-retest evaluation after belt removal and reapplication demonstrated that the correlation between two repeated CAPEIT estimates was just as strong at the kidney plane (R2 = 0.98, p < 0.001) as it was at the conventional liver plane (R2 = 0.97, p < 0.001). Finally, in an independent clinical cohort, kidney-plane CAPEIT estimates were significantly higher in participants with a high metabolic liver-risk profile (i.e. diabetes and high blood pressure) (p < 0.005). CAPEIT estimates also distinguished high and low metabolic risk groups with an AUC of 0.756. Together, these findings support the feasibility of a portable multi-organ EIT imaging framework capable of extracting complementary liver and kidney information from a single belt placement.

bioengineering↗

bioRxiv2023

Simultaneous PET and molecular MR imaging of cardiopulmonary fibrosis in a mouse model of left ventricular dysfunction

BackgroundAging-associated left ventricular (LV) dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in an LV dysfunction model. MethodsLV dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone (SAMP8) mice, a subset of mice received sham surgery. Three weeks post-surgery, mice underwent simultaneous PET-MR imaging at 4.7 T. Collagen-targeted PET and fibrogenesis MR probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio (MMR, LMR). Percent signal increase (%SI) and {Delta}LMR were computed from the pre-/post-injection MR images. Tissue specimens were analyzed for hydroxyproline (Hyp) and allysine content. Ventricular structure and function were measured by echocardiography and hemodynamic pressure-volume (PV) loop analysis. ResultsAllysine in the heart (22{+/-}5 (TAC), 13{+/-}5 (sham) nmol/g, P=0.02) and lungs (7.5{+/-}4 (TAC), 5.8{+/-}2 (sham) nmol/lung, P=0.17) of TAC mice corresponded to an increase in myocardial MRI %SI (29{+/-}15 (TAC), 6.1{+/-}4 (sham), P<0.0001) and {Delta}LMR (0.3{+/-}0.1 (TAC), 0.08{+/-}0.1 (sham), P<0.0001). Hyp in the heart (555{+/-}90 (TAC), 400{+/-}80 (sham) {micro}g/g, P<0.0001) and lungs (189{+/-}63 (TAC), 143{+/-}31 (sham) {micro}g/lung, P<0.01) were elevated in TAC mice, which corresponded to an increase in PET signal (MMR: 1.8{+/-}0.1 (TAC), 1.6{+/-}0.2 (sham), P=0.02; LMR: 1.5{+/-}0.1 (TAC), 1.2{+/-}0.1 (sham), P<0.001). PV loop and echocardiography demonstrated adverse LV remodeling, function, and increased right ventricular systolic pressure in TAC mice. ConclusionsAdministration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-MRI signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-MR imaging protocol.

molecular biology↗

bioRxiv2023

Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases

During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small molecule magnetic resonance (MR) probes that contain -effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis noninvasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, make them strong candidates for clinical translation.

biochemistry↗