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Updated: Dec 24, 2025
Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and
Christina J MacAskill1, Bernadette O Erokwu1, Michael Markley2
1Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.
Background:
Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy.
Methods:
In this study, animal and human magnetic resonance imaging (MRI) scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild-type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer.
Results:
Mean kidney T1 and T2 relaxation times showed significant increases with age (p < 0.05) as well as significant increases in comparison to WT mice (p < 2 × 10-10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p = 0.030) and T2 (p = 0.054) as a function of total kidney volume, respectively. Initial magnetic resonance fingerprinting assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer.
Conclusions:
These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD.
Impact:
A major roadblock for implementing clinical trials in patients with ARPKD is the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy. A clinical need exists to develop a safe and sensitive measure for kidney disease progression, and eventually therapeutic efficacy, for patients with ARPKD. Mean kidney T1 and T2 MRI relaxation times showed significant increases with age (p < 0.05) as well as significant increases in comparison to WT mice (p < 2 ×10-10), indicating that T1 and T2 may provide sensitive assessments of cystic changes associated with progressive ARPKD kidney disease. This preclinical and initial clinical study suggests that MRI-based kidney T1 and T2 mapping could be used as a non-invasive assessment of ARPKD kidney disease progression. These non-invasive, quantitative MRI techniques could eventually be used as an outcome measure for clinical trials evaluating novel therapeutics aimed at limiting or preventing ARPKD kidney disease progression.
Insights
Magnetic resonance imaging (MRI) T1 and T2 relaxation times show promise for tracking kidney disease progression in autosomal recessive polycystic kidney disease (ARPKD). These quantitative MRI measures may enable future clinical trials for ARPKD patients.
Area of Science:
- Biomedical Imaging
- Medical Physics
- Genetics
Background:
- Autosomal recessive polycystic kidney disease (ARPKD) is a rare, severe genetic disorder characterized by kidney cysts.
- Current clinical trials for ARPKD are hindered by a lack of sensitive measures for disease progression and treatment efficacy.
Purpose of the Study:
- To investigate the potential of quantitative magnetic resonance imaging (MRI) T1 and T2 relaxation times as biomarkers for ARPKD kidney disease progression.
- To assess the feasibility of using MRI relaxometry in both preclinical (mouse models) and initial clinical settings for ARPKD.
Main Methods:
- Utilized both animal (bpk mice) and human MRI scanners to acquire quantitative kidney T1 and T2 relaxation time maps.
- Compared data from excised kidneys of bpk mice and wild-type (WT) mice.
- Acquired MRI data from a pediatric patient with ARPKD and a healthy adult volunteer.
Main Results:
- Mean kidney T1 and T2 relaxation times significantly increased with age and in comparison to WT mice.
- Observed significant linear correlations between mean kidney T1/T2 relaxation times and total kidney volume.
- Initial assessments in an ARPKD patient showed elevated kidney T1 and T2 compared to a healthy volunteer.
Conclusions:
- Renal T1 and T2 relaxometry show potential as outcome measures for assessing cystic kidney disease progression in ARPKD.
- These quantitative MRI techniques offer a non-invasive approach for monitoring ARPKD.
- The findings support the use of MRI-based T1 and T2 mapping in future clinical trials for ARPKD therapeutics.
