Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast -Magnetic Resonance Fingerprinting (DC -MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.Over the past 3 decades, Magnetic Resonance Imaging (MRI) has become an essential medical imaging modality due to its exceptional soft tissue contrast and lack of ionizing radiation. Along with a wide variety of endogenous tissue contrast mechanisms, many MRI applications utilize an intravenous injection of an MRI contrast agent (e.g., gadolinium chelates or iron oxides) to enable sensitive identification of numerous pathologies such as tumors 1 , vascular abnormalities 2 , and cardiac infarcts 3 through local alterations in the tissue's magnetic properties (T1 and T2 relaxation times). Clinical use of these contrast-enhanced MRI scans has further expanded as multiple contrast agents have been approved for specific clinical imaging applications (e.g., blood pool contrast agents 4 , hepatobiliary contrast agents 5 ).With the emergence of the field of molecular imaging, there has been a dramatic increase in the number of MRI contrast agents targeted to proteins 6-8 , cell receptors 9, 10 , and other molecular species 11,12 . In addition, a number of activatable agents have been described that have different relaxivities based on the local tissue environment in vivo 13,14 . In a typical preclinical molecular MRI study, the T1 or T2 relaxation time (or MRI signal intensity) is
Magnetic resonance fingerprinting provides the opportunity for dynamic quantification of contrast agent distribution in preclinical tumor models on high-field MRI scanners.
BackgroundAutosomal recessive polycystic kidney disease (ARPKD) is associated with significant mortality and morbidity, and currently, there are no disease-specific treatments available for ARPKD patients. One major limitation in establishing new therapies for ARPKD is a lack of sensitive measures of kidney disease progression. Magnetic resonance imaging (MRI) can provide multiple quantitative assessments of the disease.MethodsWe applied quantitative image analysis of high-resolution (noncontrast) T2-weighted MRI techniques to study cystic kidney disease progression and response to therapy in the PCK rat model of ARPKD.ResultsSerial imaging over a 2-month period demonstrated that renal cystic burden (RCB, %)=[total cyst volume (TCV)/total kidney volume (TKV) × 100], TCV, and, to a lesser extent, TKV detected cystic kidney disease progression, as well as the therapeutic effect of octreotide, a clinically available medication shown previously to slow both kidney and liver disease progression in this model. All three MRI measures correlated significantly with histologic measures of renal cystic area, although the correlation of RCB and TCV was stronger than that of TKV.ConclusionThese preclinical MRI results provide a basis for applying these quantitative MRI techniques in clinical studies, to stage and measure progression in human ARPKD kidney disease.
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