Ureteropelvic junction obstruction (UPJO) is an impairment of urine flow from the renal pelvis into the proximal ureter and is the most common cause of hydronephrosis in neonates. This disorder is detected in up to 7% of all maternal ultrasound scans, and an estimated 10% of these newborns have hydronephrosis, which, if left untreated, may result in early failure of functional renal development in these patients. Current methods of assessing kidney function in neonates and children are less than optimal, however. While the current reference standard, nuclear renography (MAG3), yields some useful diagnostic information; it is invasive, slow, provides low resolution, does not offer anatomic detail, and delivers potentially harmful ionizing radiation. Thus, there is an urgent, unmet need to develop a method for functional imaging of kidneys that is non-invasive, safe, accurate, reproducible and radiation-free. The primary objective of this exploratory, two-year study, therefore, is two-fold: first, to develop advanced methods of motion-compensated, high spatial and temporal resolution magnetic resonance imaging (MRI) for the improved quantification of the glomerular filtration rate (GFR), an important marker of renal function; and second, to demonstrate the superiority of this method over the current reference standard, nuclear renography (MAG3). Our application in response to PAR-18-743 is specifically aimed at developing, and evaluating motion-robust, high spatiotemporal resolution dynamic contrast-enhanced MRI (DCE-MRI) for quantifying GFR (MR-GFR) as well as creating new automated analysis software to enable the robust and reproducible assessment of differential renal function in newborns eliminating need for sedation, and in older children. Our method will overcome the technical challenges of current DCE-MRI techniques providing high temporal resolution to capture fast arterial input function dynamics required for accurate computation of GFR, compensate for unavoidable respiratory and bulk motion to reconstruct high quality images and will provide robust, fast, automated post processing techniques for accurate GFR computation. As a non-invasive, motion-robust, radiation-free imaging technique that can depict renal structures at much higher resolution, MR-GFR will offer, for the first time, a level of diagnostic information that is unattainable with MAG3. The critical importance of understanding the extent and severity of UPJO (and resulting hydronephrosis) cannot be understated; for in the absence of this information, children who stand to benefit from immediate surgery might be overlooked or delayed in receiving treatment; and those who might benefit from a more conservative approach (i.e., watching waiting) might receive an unnecessary surgical intervention. Indeed, this novel imaging approach is expected to substantially improve clinical decision-making. The successful completion of our aims will enable 1) assessment of renal function accurately; 2) predicting the likelihood of functional decline; and 3) determining whether surgery is indicated. DCE-MRI is expected to have rapid translational impact for several diseases effecting kidney function once it is introduced into clinical practice.
This project addresses the need to develop advanced methods of magnetic resonance imaging (MRI) to assess kidney function in newborns and in older children who have been diagnosed with ureteropelvic junction obstruction (UPJO), an impairment of urine flow that is the most common cause of hydronephrosis (inability to void urine). Unfortunately, severe hydronephrosis, left untreated, can result in permanent damage to the child's kidneys and our novel method of assessing kidney function, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), promises to evaluate the extent of this disorder in a way that is highly accurate, non- invasive, safe, reliable, and radiation-free and will eliminate the need of repeated scans, sedation and anesthesia when imaging newborns with congenital hydronephrosis. Most importantly, this approach will enable the clinician to confidently and quickly refer children for corrective surgery based on imaging results; and likewise, recommend other children for more conservative ?watchful-waiting?, effectively reducing the number of unnecessary surgeries.