Abdominal & Pelvic MRI | Noworolski Lab

MRI and MRS of the Liver

Normal vs NAFLD SpectThe Liver MR imaging group is investigating the role MR imaging, including diffusion weighted imaging and MR spectroscopy, can play in noninvasive assessment of nonalcoholic fatty liver disease (NAFLD) and in changes in the liver and in metabolism due to diet. In particular, we are looking at assessing grades of steatosis and inflammation and the stage of fibrosis in the liver. We have several ongoing studies that include in vivo MR imaging of patients who are going on for a biopsy. In addition to the in vivo MR data, we have clinical and pathological information on these patients, many of whom are part of the UCSF site of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), an NIH, NIDDK funded, multicenter study. We are also obtaining high resolution magic angle spinning (HRMAS) spectroscopy from liver tissue samples to help guide our in vivo efforts. Currently, fatty liver disease is definitively diagnosed and assessed using invasive biopsies. In view of the high population prevalence of NAFLD, a non-invasive mode of distinguishing the relatively benign condition of simple fatty liver (or steatosis) from the more progressive form, Non Alcoholic Steatohepatitis (NASH) would be preferable and very broadly applicable. Our preliminary data shows striking MR differences between normal and diseased patients and among the different grades of steatosis, demonstrating the potential promise of MR for the noninvasive evaluation of fatty liver disease.

Publications

  1. Gugliucci A, Lustig RH, Caccavello R, Erkin-Cakmak A, Noworolski SM, Tai VW, Wen MJ, Mulligan K, Schwarz JM. Isocaloric fructose restriction lowers apoC-III levels and yields less atherogenic lipoprotein profiles in children with obesity and metabolic syndrome. Atherosclerosis. 2016. EPub. July 16, 2016. (PMCID: In Process).
  2. Lustig RH, Mulligan K, Noworolski SM, Tai VW, Wen MJ, Erkin-Cakmak A, Gugliucci A, Schwarz JM. Isocaloric fructose restriction and metabolic improvement in obese children with metabolic syndrome. Obesity. 2016 Feb;24(2):453-60. doi: 10.1002/oby.21371. (PMCID: PMC4736733).
  3. Schwarz JM. Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, Herraiz LA, Bergeron N, Bersot TP, Rao MN, Schambelan M, and Mulligan K. Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat. J Clin Endo Metab. 2015 100(6):2434-2442. DOI: http://dx.doi.org/10.1210/jc.2014-3678. (PMCID: PMC4454806).
  4. Eatesam M, Noworolski SM, Tien PC, Nystrom M, Dodge JL, Merriman RB, Qayyum A. Liver Diffusivity in Healthy Volunteers and Patients with Chronic Liver Disease: Comparison of Breath-hold and Free-breathing Techniques. J of Mag Res Im. 35(1):103-109. 2012. (PMID: 22034200).
  5. Qayyum A, Nystrom M, Noworolski SM, Chu P, Mohanty A, Lo C, Merriman R. MRI steatosis grading: Development and Initial Validation of a color mapping system. AJR Am J Roentgenol. 198(3):582-588. 2012. (PMID: 22357996)
  6. Noworolski SM, Lam M, Merriman RB, Ferrell L, Qayyum A. Estimation of Steatosis with MRS and MRI: Validation with Histology is Confounded by Differences in Methodology. Radiology. 264:88-96. 2012.
  7. Ghotb A, Noworolski SM, Madden E, Scherzer R, Qayyum A, Pannell J, Ferrell L, Peters M, Tien PC. Adipose Tissue and Metabolic Factors Associated with Steatosis in HIV/HCV coinfection: Histology versus Magnetic Resonance Spectroscopy.  J Acquir Immune Defic Syndr. 55(2):228-231. 2010.
  8. Schwarz J-M, Noworolski SM, Lee GA, Wen M, Dyachenko A, Prior J, Weinberg M, Herraiz L, Rao M, Schambelan M, Bergeron N, Mulligan K. Effects of short-term feeding with high- versus low- fructose isoenergetic diets on hepaticde novolipogenesis, liver fat content and glucose regulation. Proc of the American Diabetes Association Annual Meeting. Diabetes. 58: S382-S383. 2009.
  9. Noworolski SM, Tien PC, Merriman R. Vigneron DB, Qayyum A. Respiratory Motion-Corrected Proton Magnetic Resonance Spectroscopy of the Liver. Magn Reson Im. 27(4): 570-576. 2009.
  10. Bahl M, Qayyum A, Westphalen AC, Noworolski SM, Chu B, Ferrell L, Tien PC, Bass N, Merriman RB. Liver steatosis: investigation of opposed-phase T1-weighted liver MR signal intensity loss and visceral fat measurement biomarkers. Radiology. 249(1): 160-6. 2008. (PMCID: PMC2657853).
  11. Noworolski SM, Mulligan K, Wen M, Herraiz L, Weinberg M, Lee GA, Schwarz J-M. Short-term Dietary Effects on Liver Lipids Measured with 3T MRS. Proc of the Intn’l Soc of Mag Res in Med. 2699. 2008

Abdominal/Pelvic MRI Research Directions

Diffuse Liver Disease

Goals:

  • Developing techniques for proton MR spectroscopy of the liver which do not suffer from respiratory motion artifacts
  • Understanding the roles of in and out of phase MR imaging, proton MR spectroscopy, and MR diffusion weighting imaging play in detecting fatty liver disease and in discriminating among grades of steatosis, inflammation, and fibrosis.
  • Using HRMAS spectroscopy of liver biopsy or other liver tissue samples to understand the MR visible compounds in normal and diseased liver

Sponsor:

  • NIH/NIDDK

Grants:

“Novel Magnetic Resonance Imaging And Spectroscopy In The Non-Invasive Histologic Evaluation Of Non-Alcoholic Fatty Liver Disease”

NIH/NIDDK

PI: Bass

Dates: 10/04 - 9/05

“Non-Invasive Evaluation of Pathology and Prediction of Outcome in Non-Alcoholic Fatty Liver Disease: Role of MR Imaging and Spectroscopy.”

2003 Wylie J. Dodds Award - Society of Gastrointestinal Radiologists 

PI: Qayyum

Dates: 4/03 – 3/04

“Evaluation of MRI & MR Spectroscopic Markers in Non-Alcoholic Fatty Liver Disease”

NIH/NIDDK: R01DK074718-01A1

PI: Qayyum

Dates: 8/1/07-7/31/2013        

Liver, Nutrition, and Carbohydrates (LINC)

Goals:

  • Determine the effect of diet on fat content in the liver

Sponsor: 

  • NIH, ADA
  • A Dietary Intervention Research Program

Overview

Non-alcoholic fatty liver disease (NAFLD) leads to the accumulation of fat in the liver or steatosis. NAFLD affects up to one third of the population.  Its prevalence is rising and parallels the increasesin obesity and type-2 diabetes.  The purpose of this research program is to determine the effects of diet on fat content in the liver.

Spectrum of NAFLDProgram Summary

Locations:

-San Francisco General Hospital (SFGH)
-CTSI Clinical Research Center (CCRC)

Eligibility:

-Male or Female aged 18-60 years
-Diagnosed with steatosis as a result of NAFLD
-Females who are not pregnant or nursing
-HIV negative, Hepatitis B/C negative

Phase 1: Baseline Evaluation

Assess current status and dietary habits.

Duration:

-One inpatient stay of 4 nights and 4 days at SFGH-CCRC

Requirements:

-Provide multiple blood draws
-Eat and drink all food provided
-Receive magnetic resonance scan (MRS/MRI) to determine liver fat
-Receive Dual energy x-ray absorptiometry (DEXA) to determine full body composition
-Wear portable glucose meter for up to 7 days

-Compensation for completion of Phase 1: $600.00

If qualified, move onto Phase 2 

Phase 2: Dietary Intervention

Consume a weight loss diet lower in calories and of a specific nutrient composition.  After the 7 week diet, we will repeat a protocol similar to Phase 1 to determine the effects of the dietary intervention on steatosis.

Duration:
-7 week outpatient followed by one inpatient stay of 5 days and 5 nights, similar to Phase 1.

Requirements:
-We will provide you with all meals and snacks for seven weeks.  You must eat all study formulated food and drinks provided.
-Unable to eat food outside the study diet provided.
-No alcohol or calorie containing beverages.
-Receive a pedometer to wear for the duration of the program to track physical activity; the pedometer is yours to keep at the end of the program.
-Wear portable glucose meter for up to 7 days.

-Compensation for completion of Phase 2: $1400.00 

FAQs

Q: Does it cost me anything to be a part of the program?
A: There is no cost aside from the time commitment and cost of transportation to SFGH-CCRC.

Q: What are the benefits of participating in the program?
A: You may benefit from nutritional education and information regarding your actual food intake.  If you qualify and participate in Phase 2, adherence to the study diet should promote weight loss due to a 25% decrease in caloric intake.

Q: How many nights do I have to stay in the hospital?
A: There are two inpatient stays, during Phase 1 and at the end of the 7 week program during Phase 2.  You are required to stay at the CCRC during this time for a total of 4 nights for Phase 1 and 5 nights for Phase 2.

Q: Is there any risk with the DEXA?
A: There is some risk associated with the exposure to x-rays, but the exposure is 1/100th less than a regular x-ray.

Q: What is the risk associate with the MRS?
A: One of the greatest risks is if you have any metal containing objects in your body.  If you have metal containing objects (pacemakers, etc.) you cannot participate in the program.

Q: How much blood will I have to give?
A: The total amount of blood is less than 1 pint per inpatient stay.  The amount is within Red Cross guidelines.

Q: How will I get the food?
A: Your meals will be prepared fresh every two days.  You can come pick them up weekly at the CCRC and Research Staff will deliver meals to your house.

Q: What kind of diet will I be on?
A: All food provided for you will be made specifically for you in the CCRC research kitchen.  You will receive a diet composed of a specific nutrient composition.  The diet will consist of a 25% decrease in calories to promote weight loss.

Q: Can I stop being in the program at any time?
A: Yes.  You can stop at any time.  Also, you can be withdrawn from the program at any time if the study doctors believe it is in your best interest, or if you do not follow study protocol.  Compensation will be prorated to reflect your contribution to the study.

 Participation in research is voluntary.  If you refuse to participate there is no penalty or loss.

If interested in volunteering or for more
information, please contact:
(415) 206-5532
(510) 325-2391
[email protected]

Funded by National Institutes of Health
and American Diabetes Association

Visceral Adiposity, HIV and HCV

Goals:

  • Determine the relationship of visceral adiposity, HIV, HCV and its metabolic and inflammatory consequences on hepatic steatosis and its progression.

Sponsor:

  • NIH/NIAID

SHINE Study

Goals:

  • A novel 6-month weight loss program aimed at helping people make healthy diet and exercise lifestyle changes.

Sponsor:

  • NIH
  • UCSF Osher Center for Integrative Medicine.


Shine study at UCSF Osher Center for Integrative Medicine

Grants

Visceral Adiposity, HIV, and HCV: Biologic Mediators of Hepatic Steatosis

R01 AI087176 (Tien)                                                 

The goals of this grant are to assess the effects of visceral fat, HIV and HCV infection on hepatic steatosis.

Evaluation of MRI & MR Spectroscopic Markers in Non-Alcoholic Fatty Liver Disease

R01 DK074718 (Qayyum)

The goals are this grant are to determine if MR imaging, spectroscopy and diffusion imaging correlate with steatosis, necroinflammation and fibrosis in NAFLD and to determine if MR imaging measures of visceral fat correlate with histopathologic parameters of disease severity.

De Novo Lipogenesis in the Pathogenesis of Non-Alcoholic Fatty Liver Disease

R01 DK078133 (Schwarz; Touro University)

The major goal of this project is to assess how a diet preventing hepatic de novo lipogenesis can reduce liver fat content in steatotic patients.

Metabolic Impact of Fructose Restriction in Obese Children

R01 DK089216 (Schwarz; Touro University)

The goals of this grant are to assess the effects on metabolism of reducing fructose intake in an obese pediatric population.

Metabolic and Immunologic Effects of Meditation

P01 AT005013 (Hecht, F.)

The major goal of this study is to test the effects of adding a meditation component aimed at reducing stress and increasing awareness of eating behaviors to diet and exercise in obese persons. In addition to a clinical trial, the proposal will test the effects of meditation on stress hormone patterns, metabolic pathways, and immunologic responses.

Research Patient/Volunteer Information

Most studies are currently done on the 3T research MR scanner at the UCSF Center for Molecular and Functional Imaging (CMFI).

Volunteer Qualifications

If any of the following apply to you, you may not be a candidate for the liver MRI/MRS exam, part of the exam may not be able to be performed, or the quality of your data may be compromised.

Please call (415) 353-9409

  1. Vascular clips (Brain).
  2. Vascular clips (Other than brain-okay, after six months).
  3. Severe claustrophobia.
  4. Cardiac Pacemaker.
  5. Metal in eye (previous or current).
  6. Any other metallic or foreign object in body. Please check with us or your physician prior to your appointment.

Volunteer Preparation

  1. Arrive 30 minutes before the time of your appointment to provide yourself time to complete the MRI screening form, read and sign the consent form, change and prepare for the exam.
  2. If you are claustrophobic and require sedation, please bring the sedation with you. We suggest that sedatives be taken about 1/2 hour before the start of the examination, or as prescribed by your physician.

Patient Procedures

Upon arrival to the CMFI MRI scanner, patients should first check in with the receptionist at the front desk. A research associate will come to the waiting room to talk with the patient and answer any questions the patient might have before the exam. After the paperwork is in order, the patient will be shown to the changing area and instructed to change into hospital attire and store all of his/her personal belongings in a secure locker. After changing, the patient should wait in the changing room until someone brings him/her to the MRI exam room. Any patient who has brought prescription sedatives with him/her needs to talk to the MRI technician before taking the sedatives (which should be about 1/2 hour before the start of the examination).

When the patient is brought back to the exam room, he/she will be instructed to lie down on the MRI bed. A coil device will be strapped to the patient's abdomen. The patient will be given earphones or earplugs to help block out noise from the scanner, and moved into the MRI tube.

During the examination, there is a communication system set up between the control room and the patient. In order to get the best images and data, the patient needs to remain motionless and relaxed during the entire examination, which lasts about 50 minutes. If the patient has a question, concern or non-emergency problem during the exam, he/she should wait for a break between image acquisition sequences to address the technician in the control room. Some of the image acquisition sequences will require the patient to hold his/her breath for about 20 seconds. The technician will instruct the patient about this. As soon as the examination is over, the patient will be removed from the MRI tube. After this, the patient may return to the changing room, retrieve his/her personal belongings and then leave.

 

The Noworolski Laboratory is focused on translational MR imaging of the abdomen and pelvis. We focus two general areas of multiparametric MRI studies. The first is on prostate cancer, including quantitative modeling of the MR data and AI/ML approaches to identify and predict cancer aggressiveness. The second is on studies of metabolic health, including liver, visceral, and pancreatic fat measures, and novel measures of fat, to assess metabolic health in high-risk patients and after interventions, particularly dietary interventions.

Research Directions

Prostate Cancer MRI

Multiparametric MRI of Prostate Cancer – Correlations with Histopathology

Multiparametric MRI of Prostate Cancer – Correlations with Histopathology

The Noworolski Lab has a long history of establishing the mpMRI signatures of cancerous and various benign tissues, with detailed correlation with histopathology. In recent years, this has been focused on the prostate – for both identifying cancer and for distinguishing aggressive prostate cancer from indolent cancer. Based upon these analyses, we have generated cancer risk maps and aggressive cancer risk maps.

References:
  1. Starobinets O, Simko J, Kuchinsky K, Kornak J, Carroll PR, Greene KL, Kurhanewicz J, Noworolski SM. Characterization and Stratification of Prostate Lesions Based on Comprehensive Multiparametric MR Imaging Using Detailed Whole Mount Histopathology as a Reference Standard. NMR Biomed. 2017; 30(12). DOI: 10.1002/nbm.3796. (PMCID PMC9592076).
  2. Gibbons M, Starobinets O, Simko JP, Kurhanewicz J, Carroll PR, Noworolski SM. Identification of Prostate Cancer Using Multiparametric MR Imaging Characteristics of Prostate Tissues Referenced to Whole Mount Histopathology. Magn Reson Imaging. 2022 Jan;85:251-261. Doi: 10.1016/j.mri.2021.10.008. PMCID: PMC9931199.
  3. Gibbons M, Simko JP, Carroll PR, Noworolski SM. Prostate Cancer Lesion Detection, Volume Quantification and High-grade Cancer Differentiation using Cancer Risk Maps Derived from Multiparametric MRI with Histopathology as the Reference Standard. Magn Reson Imaging. 2023. https://doi.org/10.1016/j.mri.2023.01.006

Prostate Cancer Risk Maps to Predict Progression

Prostate Cancer Risk Maps to Predict Progression

We are utilizing our prostate cancer risk maps to identify and predict progression for men on active surveillance. We are additionally investigating utilizing the maps to predict biochemical recurrence of prostate cancer after prostatectomy.

Prostate Cancer Risk Maps to Plan High Intensity Focused Ultrasound (HIFU) Treatment for Prostate Cancer

Prostate Cancer Risk Maps to Plan High Intensity Focused Ultrasound (HIFU) Treatment for Prostate Cancer

We are investigating whether our prostate cancer risk maps can better target therapy for men receiving HIFU treatment for prostate cancer. 

Computer Aided Diagnostic System for Prostate Cancer Detection Using Quantitative Multiparametric MRI

Computer Aided Diagnostic System for Prostate Cancer Detection Using Quantitative Multiparametric MRI

With Principal Investigator, Greg Metzger, from the University of Minnesota, we are developing a prostate imaging phantom and analyses tools and performing multi-center, multi-vendor quantitative imaging technical performance evaluations for imaging the prostate.

Metabolic Health MRI