Liver Imaging Research Program

Liver diseases represent an unrecognized but exploding epidemic and a rapidly increasing cause of chronic disease and health-care utilization in Canada. For example, about 1 in 3 Canadian adults and 1 in 10 children have fatty liver disease not caused by alcohol intake. These numbers become much higher among the 50% of Canadians who are obese, of whom three-quarters have fatty liver disease. While this disease initially has no symptoms, up to a quarter of these people will develop serious liver symptoms that can ultimately progress irreversibly into cirrhosis, liver cancer or complete liver failure, requiring liver transplantation. Currently, there is no readily accessible diagnostic test to predict the progression of fatty liver disease.  Given the growing obesity epidemic, particularly among children and teenagers, the long term implications for individual and population health of non-alcoholic fatty liver disease are substantial.

Liver image and blood flow maps from dynamic contrast enhanced CT scan after respiration corrections: (A) averaged CT scan, (B) total (arterial and venous) blood flow and (C) arterial blood flow

Assessment of Liver and Abdominal Fat

The only method currently available to assess liver fat content is needle biopsy, which is invasive, painful, costly, occasionally unreliable, and has significant risks. The US National Institutes of Health (NIH) has stated that “one of the roadblocks to therapeutic studies in … fatty liver disease is the need to perform liver biopsies …”

The liver imaging research group is part of an international industrial-academic partnership that is developing methods to assess liver fat with MRI. With support from GE Healthcare and Canadian funding agencies, the team is now testing their techniques in patients with various forms of fatty liver disease. Their ultimate goal is to show that our non-invasive MRI fat measurement technique is equivalent or even superior to the invasive liver biopsy, and can therefore replace this diagnostic method. This could significantly improve the ability to diagnose and monitor patients with this common health problem, resulting in improved quality and quantity of life from many viewpoints. 

Obesity is a risk factor for fatty liver disease, and it is well known that not only is the total amount of fat important, but so is the distribution of that fat. In particular, fat that is inside the body (visceral fat) is more important than fat carried just under the skin (subcutaneous fat) for predicting the likelihood of liver disease, as well as cancer, diabetes and heart disease. For this reason, the liver imaging group has been developing methods for imaging the 3D distribution of fat in the abdomen and for automatically distinguishing visceral fat from subcutaneous fat. This is a significant advance on current fat measurement methods that require time consuming manual image analysis.

The ultimate goal of this work is create a method of measuring internal and subcutaneous fat volumes over the entire body. This would significantly improve the ability to asses a patients risk for diseases like heart disease and determine which patients need immediate and intensive intervention and which are better candidates for simpler and cheaper lifestyle and dietary interventions.

Assessment of Liver Iron 

Excessive iron can be deposited in the liver as a result of a number of relatively common genetic diseases, as well as a result of multiple blood transfusions (e.g. following major surgery). This excess iron can impair liver function, and if left untreated can result in liver failure. In patients with iron-overload but no liver fat, MRI is the gold standard to quantify liver iron content. However, many patients with fatty liver disease also have significant iron deposition in the liver. While existing MRI techniques can detect and possibly measure liver fat or iron-overload in isolation, no non-invasive method exists for accurately determining fat fraction and iron concentration simultaneously, because the effects of fat and iron on the MRI image can cancel each other out. This leaves a painful and expensive liver needle biopsy as the only option for diagnosis. The team is currently developing an extension of their MRI fat measurement technique that will also allow measurement of liver iron content, even in the presence of significant liver fat. Their ultimate goal is to improve this MRI technique until it is capable of eliminating needle biopsies in another large group or patients.

Monitoring of Disease Treatment

Few options exist for treating patients with fat and/or iron deposition in the liver. The group is beginning to evaluate our MRI techniques as an alternative to biopsy to monitor patients’ response to treatment. Widespread use of the techniques being developed by BIRC scientists could significantly accelerate the development of treatments for these common and complex liver conditions.

Developing new liver imaging techniques has assumed renewed priority recently, due to the widespread prevalence of these diseases and the risk of serious downstream complications that will require highly sensitive and specific non-invasive and cost-effective tools for diagnosis and monitoring progression and response to treatment. Our investigators are developing the next generation of MRI techniques for use in animal studies and clinical trials. Over the next decade, imaging will play a pivotal role in the development of effective new treatments for liver disease.

Multi-Modality Guided Focal Liver Ablation

Hepatocellular carcinoma (HCC) is the fifth most common diagnosed malignancy and the third most frequent cause of cancer related deaths worldwide, and it has a wide geographical variation. Incidence is particularly high in Asia and sub-Saharan Africa due to the large incidence of hepatitis B and C, both of which are complicated by hepatic cirrhosis. Recently, increasing trends in HCC have been reported from several Western countries. Furthermore, the liver is the second most common site of metastatic cancer arising in other organs.

Although the most effective method of treating liver cancer is surgical resection, about two-thirds of liver cancer patients have non-resectable tumour at diagnosis because of the size or location of the tumour. For some of these patients, focal ablative therapy, particularly radiofrequency or micro-wave (thermal) ablation, then becomes the treatment of choice. The current standard of care uses CT images for planning and 2D ultrasound image guidance for intra-operative guidance of the ablation probe(s) into the target lesion. However, this approach suffers from several disadvantages, which we propose to overcome by the development of 3D ultrasound (3D US) imaging, registered with pre-procedural CT to plan and guide the ablation procedure.

The goal is to develop a 3D US-guided system able to accommodate any US transducer for acquiring 3D US images and guiding therapy applicators. Our guidance technology promises to show the features of liver masses and the hepatic vasculature more clearly, and allow guidance of the ablation probes to the target more accurately. This 3D US-guided approach will allow more accurate monitoring of the ablation zone during the procedure and at follow up.

Quantitative Blood Flow Imaging

Anti-angiogenesis therapy (e.g. Sorafenib), stereotatic ablative body radiotherapy and trans-arterial chemo-embolization are also being employed and investigated for treatment of primary and liver metastases.  These treatments are dependent upon or affect tumour blood flow. Therefore, being able to quantitatively assess tumour blood flow at baseline potentially can allow for treatment response prediction, and monitoring change in blood flow will allow early assessment of treatment response.

Liver has a dual blood supply – the hepatic artery supplies oxygenated blood and the portal vein carries blood containing nutrients along with toxins from the digested food in the intestines. Current practice is tri-phasic contrast enhanced CT imaging, taking three snapshots before, during and after contrast injection. Employing dynamic contrast enhanced CT imaging along with breathing motion correction algorithms, we are now able to quantify the arterial blood flow and separately the venous blood flow. In fact, we found that different tumours have different amount of arterial blood flow. The arterial blood flow is usually elevated in and around the tumours while the venous blood flow is decreased within the tumours. The ability to quantify tumour blood flow allows us to perform research on treatment response prediction and early response monitoring.  

Investigators
Paul Adams, MD, Iron Overload
Melanie Beaton, MD, Liver Disease
Rob Hegele, MD, Genetics and Endocrinology
Tisha Joy, MD, Endocrinology Lipodystrophy
Charles McKenzie, PhD, MRI and Spectroscopy
Elaine O’Riordan, MD, Liver Imaging
Ting Lee, PhD, Imaging Scientist
Michael Lock, MD, Radiation Oncologist
Barbara Fisher, MD, Radiation Oncologist
Eugene Wong, PhD, Medical Physicist
Roman Kozak, MD, Radiologist
Nirmal Kakani, MD, Interventional Radiologist
Amol Mujoomdar, MD, Interventional Radiologist