San Antonio (TX), Bolton (MA)
Until recently, diffusion weighted magnetic resonance imaging (MRI) has been exploited to greatest advantage in brain imaging for strokes. As a result of ongoing technical improvements in gradients and imaging sequences, however, diffusion weighted MRI is becoming more and more important in evaluating disease outside the brain. In particular, diffusion weighted MRI has become an important new tool in the detection, characterization, and follow up of malignant lesions in the chest, abdomen, and pelvis.
Whereas conventional MRI focuses on providing anatomic detail, diffusion weighted MRI measures the ability of water molecules to experience unrestricted Brownian motion. In tissues, extracellular water is free to move about randomly while intracellular water molecules are limited in their motion due to complex interactions with various intracellular components and the highly compartmentalized nature of the intracellular environment. In the past, this cause of limited molecular motion (or diffusion restriction) has been exploited to great advantage in stroke imaging. Because brain ischemia causes water to move from the extracellular space to the intracellular space, the increasing volume of intracellular water results in increasing diffusion restriction within the affected tissue. This increase in average diffusion restriction is then visible on diffusion weighted imaging as an area of elevated signal with a decreased apparent diffusion coefficient (ADC).
Water moving into cells, however, is not the only tissue characteristic that may lead to elevated signal on diffusion weighted MRI. If one tissue is inherently more cellular than another, the more cellular tissue will on average have more intracellular water and will tend to demonstrate elevated signal on diffusion weighted MRI. This is of particular interest in the field of oncologic imaging since tumors and metastases tend to be composed of large and/or tightly packed cells with limited extracellular matrix when compared to surrounding normal tissues.
Another important characteristic of diffusion weighted MRI is its reliance on inherent tissue contrast rather than on the administration of intravenous contrast. This can be of particular importance in patients with renal failure or contrast allergies. In addition, diffusion weighted MRI sequences can be performed quickly due to the reliance on echo planar single shot pulse sequences, allowing for significant useful additional information to be gathered at relatively little additional imaging time expense.
In the liver, diffusion imaging is already establishing its role as an important part of the routine liver MRI. As born out by recent studies and clinical experience, it now appears to be the most sensitive non-contrast sequence available for the detection of focal liver lesions. In particular, low B value diffusion weighted sequences have been shown to be significantly more sensitive than traditional spin echo T2 fat saturated images with respect to focal liver lesion detection. In fact, for some tumors such as small carcinoid metastases, diffusion weighted imaging can sometimes be the only sequence on which the lesions are well and reliably visualized. Similarly, diffusion sequences can be of significant aid in detection and delineation of infiltrative hypoenhancing lesions such as cholangiocarcinomas.
Not only is diffusion weighted MRI useful in liver lesion detection, but it also serves as an important adjunct to contrast enhanced imaging in lesion characterization. While not completely specific, evaluation of ADC values can provide significant additional information that can aid in characterizing a focal lesion as benign versus malignant due to the tendency toward decreased ADC values in malignant lesions. Again, this can be of particular importance when post contrast imaging is not available.
Apparent diffusion coefficient analysis has also shown promise in characterizing the severity of hepatic fibrosis in patients with cirrhosis. The deposition of large amounts of collagen in the intracellular matrix results in decreased ADC values, and threshold values for stratifying degrees of fibrosis based on ADC values are currently being discussed in the literature. On the other hand, this utility in evaluation of hepatic fibrosis comes at the cost of decreased utility in evaluating the cirrhotic liver for focal lesions. Because of the increased background signal from the fibrotic liver, the characteristic small changes in ADC of malignant lesions can be obscured. Thus, the utility of diffusion MRI in screening for hepatocellular carcinoma in the cirrhotic patient is limited.
Similar to the liver, diffusion sequences are also valuable with regard to oncologic imaging in the pancreas. Pancreatic adenocarcinoma can often be difficult to detect and precisely delineate due to its infiltrative nature and poor enhancement. Because these tumors are often either densely cellular and/or surrounded by tumor induced extracellular fibrosis, however, diffusion weighted imaging can provide important additional data that can aid in detection, characterization, and measurement of the tumor mass.
Diffusion weighted MRI has also shown promise in primary characterization of breast lesions as well as in evaluation of treatment response in breast cancer. Several studies have shown that malignant lesions in the breast conform to the trend of depressed ADC values when compared to benign lesions, thus potentially aiding in lesion characterization. In addition, there is a significant and measurable increase in ADC values within tumors when they respond to chemotherapy, thus potentially allowing separation of responders versus non responders to neoadjuvant chemotherapy before significant changes in lesion size are measurable.
In the pelvis, diffusion weighted imaging has shown some utility in evaluation of prostate cancer. Although ADC values overlap between benign and malignant nodules and post biopsy hemorrhage can create obscuring artifacts, there is a significant trend toward decreased ADC values in malignant lesions. Because of this property, ADC analysis provides useful additional data when combined with other sequences such as dynamic contrast enhancement in evaluating for prostatic malignancy. Other potential uses in the pelvis include evaluation of cervical cancer, evaluation of lymph nodes for metastatic disease, and restaging of rectal cancer following neoadjuvant chemotherapy.
Of course, there are many limitations to diffusion weighted MRI with respect to tumor detection and evaluation. For example, tumors with low cellularity often do not demonstrate restricted diffusion. Similarly, hemorrhagic or necrotic tumors are also unlikely to show significant diffusion restriction. There are also technical challenges, including possible motion and susceptibility artifacts.
To download a PDF version of this article please click here.
However, despite these limitations, diffusion weighted magnetic resonance imaging has become an important tool in oncologic imaging outside the central nervous system. Continuous improvements in both scanner technology and understanding of the pre- and post-treatment properties of various tumors will increase the importance of diffusion weighted MRI in cancer detection and evaluation in the future.
About the Author
Dr. Todd Tibbetts is a board-certified radiologist at Intrinsic Imaging. He completed his M.D. and Ph.D. degrees at Baylor College of Medicine where his training was sponsored by the National Institutes of Health Medical Scientist Training Program. His doctoral degree is in cell and molecular biology and resulted in several peer reviewed, original research articles. After graduating medical school, Dr. Tibbetts completed a diagnostic radiology residency at Baylor College of Medicine then further sub-specialized in abdominal radiology at Harvard Medical School’s Massachusetts General Hospital. He is board-certified in diagnostic radiology with sub-specialized training in body imaging and a clinical focus on oncology imaging.
About Intrinsic Imaging LLC
Located in Bolton, Massachusetts and San Antonio, Texas, Intrinsic Imaging is an FDA audited, ISO 9001:2008 and ISO 13485:2003 certified, GAMP® 5 compliant medical imaging core lab specializing in providing imaging core lab services for clinical trials. Its comprehensive medical imaging core lab services include, but are not limited to, expert radiologist consultation, protocol and charter development, site qualification, training and management, as well as image acquisition, processing and detailed radiologic analysis.
Intrinsic Imaging has more than sixty full-time, board-certified diagnostic radiologists on staff that have sub-specialization in all therapeutic areas including, but not limited to, Cardiovascular, Central Nervous System, Gastrointestinal & Genitourinary, Medical Device, Musculoskeletal and Oncology.