University of Wisconsin–Madison

Current Research

On-Going Clinical Trials

Current Research Areas

  1. Quantification of Hepatic Steatosis
  2. Quantification of Hepatic Iron Overload
  3. Quantification of Perfusion in Liver Tumors
  4. Quantification of Liver Hemodynamics
  5. New Hepatobiliary Contrast Agents
  6. Improved Abdominal MR Imaging
  7. Comparison of Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) with Contrast-Enhanced Computed Tomography (CE-CT) for the Detection of Appendicitis
  8. New Techniques for Imaging near Metal
  9. Improvements in Quantitative Diffusion-Weighted Imaging

Quantification of Hepatic Steatosis

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease of both adults and children in the United States. The prevalence of hepatic steatosis likely exceeds 20% of the US and is increasing, paralleling the current epidemic of obesity and its association with metabolic syndrome and diabetes.  Early detection and treatment may halt or reverse progression to liver injury, inflammation, fibrosis and, ultimately, cirrhosis, which has dreaded complications including liver failure, portal hypertension and hepatocellular carcinoma. Liver biopsy, the current clinical gold standard to assess liver fat and diagnose NAFLD, is not conducive to the repeated measurements necessary to monitor liver disease and/or treatment because of the risk of bleeding, expense, and most importantly, poor sampling variability. LIRP currently focuses on the validation of proton density fat fraction measurements as compared to other invasive and non-invasive methods like MR Spectroscopy, Computer Tomography and Biopsy. Since fatty infiltration is known to be inhomogeneous throughout the liver, LIRP focuses also on establishing techniques evaluating the entire liver instead of single samples like MRS or Biopsy.

Quantification of Hepatic Iron Overload

Excessive accumulation of iron in the liver can affect both adult and pediatric populations. Surplus iron is toxic and requires treatment aimed at reducing body iron stores. Measurement of liver iron is critical for the detection and staging of iron overload, and for the monitoring of iron-reducing chelating therapies, which are expensive and have significant side effects. MRI is a widely available, accessible, and safe technology, and it is very sensitive to the presence of iron in tissue.  MRI-based techniques for liver iron quantification include relaxometry (measuring the rate of decay of the signal) and susceptometry (estimating the magnetic susceptibility of tissue based on its effects on the magnetic field). In this project, we are developing and validating novel relaxometry and susceptometry techniques for rapid, accurate, precise, robust, and reproducible MRI-based liver iron quantification.

Quantification of Perfusion in Liver Tumors

Funded by a American Recovery and Reinvestment Act (ARRA) grant from the NIH, this project aims to develop and validate quantitative measures of local blood flow (perfusion) to liver tumors. Increasingly, many tumors are being treated with anti-angiogenic agents such as bevacizumab and soranfenib. Although effective in many patients, these agents may not demonstrate a detectable treatment response for many months when using conventional CT and MRI methods. By quantifying blood flow to liver tumors accurately, we aim to detect changes in blood flow to tumors in 2-3 days, as an early biomarker of tumor response. This project is developing and validating novel Cartesian and non-Cartesian based methods for more accurate quantification of perfusion in liver tumors.

Quantification of Liver Hemodynamics

Non-invasive assessment of the hepatic vasculature and its hemodynamics using current approaches such as Doppler ultrasound and conventional 2D phase contrast MRI (2D PC-MRI) is challenging due to the dual blood supply to the liver and its complex and variable anatomy, specially in patients with portal hypertension. The use of 4D magnetic resonance imaging methods for assessing blood flow, allows the co-registration of anatomical and hemodynamic information in the vessels of interest. A time resolved 3D radial PC-MRI method developed in the MR flow group UW-Madison, have demonstrated feasibility of qualitative flow visualization and quantification in the abdominal circulation, with high spatial resolution and large volumetric coverage using 3D radial undersampling strategies. In general the purpose of this project is to comprehensively investigate the abdominal vasculature in patients with portal hypertension using a time-resolved 3D (“4D”) PC-MRI method featuring radially undersampling (PC-VIPR).

New Hepatobiliary Contrast Agents

In 2008, the FDA approved a new gadolinium based contrast agent, gadoxetic acid (Eovist, Bayer Pharmaceuticals, Wayne, New Jersey). Gadoexetic acid has important pharmacokinetic properties, namely the uptake of approximately 50% of the agent into functioning hepatocytes, with subsequent excretion into bile. This behavior offers new opportunities for the detection and characterization of focal liver lesions such as metastatic disease, focal nodular hyperplasia, hepatic adenoma, and hepatocellular carcinoma, as well as providing new means of functional biliary imaging for direct T1 weighted MR cholangiography. The LIRP has focussed on developing new methods and optimizing strategies the fully exploit the ability of hepatobiliary phase imaging to diagnose liver disease. Clinical studies on the performance of this agent to diagnose liver disease, when used in combination with optimized imaging approaches are also be performed.

Improved Abdominal MR Imaging

The LIRP is interested in the development and translation of new methods for improved MR imaging, particularly those related to abdominal imaging. New methods aimed at reducing scan time, improving image quality, and obtaining new information not previously available from conventional MR methods are being developed and validated. In many cases, the development and evaluation are being performed in collaboration with GE Healthcare, who is a research partner with the University of Wisconsin, Departments of Radiology and Medical Physics, and with the LIRP.

Comparison of Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) with Contrast-Enhanced Computed Tomography (CE-CT) for the Detection of Appendicitis

Appendicitis is a common cause of abdominal pain, frequently leading to presentation to the Emergency Department (ED). Clinical findings alone can incorrectly diagnose appendicitis 8-30% of the time. Conversely, failing to diagnose appendicitis has severe adverse outcomes including appendiceal rupture, abscess formation, and death. For this reason, emergency physicians and surgeons often rely on imaging technologies to assist in the diagnosis. Currently, the most widely used imaging test for the diagnosis of appendicitis in the United States is CT. However, researchers have reported increasing concerns regarding the amount of ionizing radiation exposed to patients during these scans. Alternate imaging modalities including ultrasound and MRI have been proposed as a safer choice. While MRI has been shown to accurately diagnose appendicitis in the pediatric population, its use in the general public has not been established. Therefore, this study aims to test the sensitivity and specificity of CE-MRI for the detection of appendicitis when compared to the reference standard of CE-CT. All patients age 12 and older who present to the University of Wisconsin Emergency Department and have a CE-CT ordered for the evaluation of appendicitis will be eligible for participation, barring any contraindication to MRI or gadolinium-based contrast agents. We would like to acknowledge funding from the Department of Radiology Research and Development Funds and UW’s Institute for Clinical and Translational Research Clinical and Type 1 Translational Research Pilot Grant for their support of this project.

New Techniques for Imaging near Metal

Over the past several decades, the aging population has led to an increased incidence of osteoarthritis resulting in more joint replacements and implantation of mechanical prostheses. Ideally, imaging would enable early detection of complications such as infection, synovitis, osteolysis, and implant loosening. Conventional MRI is widely used and is highly accurate for evaluation of many musculoskeletal disorders, but its use has been severely limited due to the metal-induced susceptibility changes in the B0 field. The B0 field perturbations create a wide distribution of proton resonant frequencies in adjacent tissue. Although recently developed imaging techniques greatly improve imaging near metallic implants, they suffer from in-plane spatial distortion in the frequency-encoding direction. Ultimately, any MR acquisition that uses frequency-encoding is fundamentally limited in its ability to eliminate distortion artifacts related to metal. The goal of this LIRP project is to develop and test a spectrally resolved fully phase-encoded (SR-FPE) 3D FSE technique for distortion-free imaging near metal. Acceleration methods are also being investigated, including parallel imaging acceleration in three directions, to achieve the scan time reductions necessary for clinical implementation.

Improvements in quantitative diffusion weighted imaging

Diffusion-weighted (DW) MRI is a powerful technique for assessment of tissue microstructure in healthy and diseased tissue. Unfortunately, application of DW-MRI in the body is hampered by the presence of multiple confounding factors, including: motion effects, low SNR, presence of fat, perfusion effects, as well as a number of imaging artifacts. These confounding factors limit the ability to use DW-MRI as a quantitative tool. In this project, we aim to identify and address these confounders using novel acquisition and reconstruction techniques, in order to improve the robustness, reproducibility and clinical utility of body DW-MRI.