# Impact of ischemia duration on MRI-derived perfusion parameters in a mouse kidney transplant model

**Authors:** Felix L. Herr, Sandra Kloiber-Langhorst, Ming Ming Li, Olaf Dietrich, Robert Erdelkamp, Christoph Walz, Severin Jacobi, Ulrich Wirth, Jens Ricke, Clemens C. Cyran, Joachim Andrassy

PMC · DOI: 10.1186/s41747-025-00675-x · 2026-02-04

## TL;DR

This study shows that longer cold ischemia in mouse kidney transplants causes more severe microvascular injury, which can be detected using MRI perfusion measurements.

## Contribution

The study demonstrates that DCE-MRI can noninvasively detect microvascular injury caused by prolonged cold ischemia in kidney transplants.

## Key findings

- Prolonged cold ischemia (16 hours) significantly increases vascular permeability in transplanted kidneys.
- DCE-MRI is a sensitive tool for detecting ischemia-induced microvascular dysfunction.
- Longer ischemia leads to more severe endothelial and microcirculatory injury in transplanted kidneys.

## Abstract

Cold ischemia during kidney transplantation induces ischemia-reperfusion injury with endothelial dysfunction, capillary leak, and impaired perfusion. Its duration critically determines graft outcome. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables noninvasive assessment of renal microcirculation and may indicate ischemic injury. We evaluated the impact of ischemia duration on DCE-MRI-derived perfusion parameters in renal transplants in mice.

Procedures were approved by the local institutional animal care and use committee. A total of 15 C57BL/6 mice underwent kidney transplantation and were assigned to a short or prolonged cold ischemia group. DCE-MRI was performed to assess renal perfusion. Imaging was conducted at a mean of 268 ± 30 days (mean ± standard deviation) after transplantation. Perfusion parameters were calculated using the Patlak model, which provides the plasma volume fraction (vp), reflecting renal blood volume and perfusion, and the volume transfer constant (Ktrans), characterizing the rate of contrast agent extravasation from capillaries into the extravascular extracellular space.

Significant differences were observed in the Ktrans parameter of transplanted kidneys between groups. The median Ktrans (mL/100 mL/min) was significantly higher in the 16-h group (2.87, interquartile range 2.45–3.03) versus the 30-min group (0.91, 0.90–1.42; p = 0.008). Median vp (mL/100 mL/min) was non-significantly lower in the 16-h group (21.89, 17.28–23.22) versus the 30-min group (29.02, 24.99–37.15; p = 0.151).

Cold ischemia with 16-h duration was associated with significantly higher Ktrans values in kidney transplants, reflecting significantly increased vascular permeability. DCE-MRI provides a sensitive tool for detecting ischemia-induced microvascular dysfunction.

Quantitative DCE-MRI detects microvascular injury after 16-h cold ischemia in kidney transplants in mice, supporting its potential as a noninvasive tool to assess graft integrity and guide interventions aimed at improving long-term transplant outcomes.

The duration of ischemia critically affects endothelial integrity and perfusion characteristics in a mouse kidney transplant model.Prolonged 16-h ischemia leads to increased vascular permeability, indicating more severe endothelial and microcirculatory injury in transplanted kidneys.DCE-MRI enables sensitive detection of subtle ischemia-related microvascular alterations, supporting its value for noninvasive graft assessment.

The duration of ischemia critically affects endothelial integrity and perfusion characteristics in a mouse kidney transplant model.

Prolonged 16-h ischemia leads to increased vascular permeability, indicating more severe endothelial and microcirculatory injury in transplanted kidneys.

DCE-MRI enables sensitive detection of subtle ischemia-related microvascular alterations, supporting its value for noninvasive graft assessment.

## Full-text entities

- **Diseases:** Cold ischemia (MESH:D007511), edema (MESH:D004487), hypoxia (MESH:D000860), immunological injury (MESH:D007154), glomerulosclerosis (MESH:D005921), inflammation (MESH:D007249), hypothermia (MESH:D007035), capillary dysfunction (OMIM:163000), vasculopathy (MESH:D000090122), dislocation (MESH:D004204), end-stage renal disease (MESH:D007676), pain (MESH:D010146), ischemic injury (MESH:D017202), endothelial injury (MESH:D057772), IRI (MESH:D015427), mediated (MESH:C567355), endothelial dysfunction (MESH:D014652), microvascular dysfunction (MESH:D017566), aggressiveness (MESH:D010554), ischemic (MESH:D002545), acute kidney injury (MESH:D058186), tissue injury (MESH:D017695)
- **Chemicals:** Buprenorphine (MESH:D002047), Gadobutrol (MESH:C090600), flumazenil (MESH:D005442), isoflurane (MESH:D007530), gadolinium (MESH:D005682), naloxone (MESH:D009270), atipamezole (MESH:C050701), fentanyl (MESH:D005283), medetomidine (MESH:D020926), carprofen (MESH:C007005), midazolam (MESH:D008874), creatinine (MESH:D003404), DCE (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12873054/full.md

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Source: https://tomesphere.com/paper/PMC12873054