A New Look at Crohn's Disease
A New Look at Crohn's Disease
Multiple imaging modalities are available for assessing the intestinal tract; each has strengths and weaknesses and often the tests are complementary. Endoscopy-based techniques such as colonoscopy, deep small intestinal endoscopy, and capsule endoscopy are highly sensitive, but only assess the superficial mucosal layers. Cross-sectional imaging is best for visualizing the deep layers of the gut and assessing for strictures, as well as extraluminal complications such as fistulae and abscesses. Because of its broad availability and high spatial resolution, computed tomography (CT) based imaging, especially CT enterography (CTE), has become the most widely used cross-sectional imaging technology for Crohn's disease. Intrinsic to CT technology is the radiation utilized to generate the images. Growing concern about the potential risks associated with cumulative diagnostic radiation exposure, particularly in young patients, has led to growing interest and research into new techniques to minimize radiation from diagnostic CT while maintaining diagnostic quality as well as interest in alternative imaging modalities. At the same time, improved spatial resolution of magnetic resonance (MR) based techniques, along with development of faster imaging sequences have helped overcome bowel motion-related artifacts, and have driven a rapid increase in the use of MR enterography (MRE) for Crohn's imaging. Further, ultrasound offers excellent tissue discrimination with the advantage of being relatively low cost, safe and, potentially, office based. A recent systematic review of the standard imaging modalities applied to Crohn's disease has been published that highlights advances in the field. This review will consider new and future applications of these technologies.
CTE has almost completely replaced the traditional small bowel follow through in most academic centers. The key difference between CTE and standard abdomen and pelvis CT scan lies in the use of low-density oral contrast that results in a low density of the bowel lumen compared with the standard 'white out' of barium or iodine-based oral contrast used for standard scans. In the USA, this is accomplished by the use of FDA-approved VoLumen (Bracco Diagnostics, Westbury, New York, USA) and in European centers by other agents including polyethylene glycol or administration of methylcellulose. CTE also utilizes intravenous iodinated contrast that allows excellent definition of the mucosa revealing enhancement pattern, a highly sensitive indicator of mucosal inflammation. In addition, it helps better delineate the mural stratification and allows for stricture assessment. The use of multidetector CT scanners allows the acquisition of thin axial slices with nearly isotropic voxels which is used to generate high resolution three-dimensional reconstructed images that provide insight into the distribution, nature and significance of inflammation and strictures.
The potential adverse effects of cumulative radiation dosage from diagnostic imaging have gained attention in the medical community and in the lay press. Measurement of effective radiation doses in CT is dependent on several factors, such as scanning technique and patient body habitus. One study by Jaffe et al. found that the mean effective dose for abdominopelvic multidetector CT was 16.1 mSv, which was up to five times higher than small bowel follow through examination. Recently, several changes have been introduced to CT scanning techniques that allow the acquisition of 'low-dose CT', leading to decrease in the overall dose of radiation delivered to the patient undergoing CT examination while maintaining image quality. These changes include the use of automatic tube current modulation (ATCM) and low-voltage (kVp) settings used in the CT scanner along with introduction of new image reconstruction algorithms that reduce the image noise typically associated with these techniques. Dose reduction efforts have resulted in markedly decreased radiation exposure. The most recent algorithms have the potential to reduce radiation exposure from CT scanning below 1 mSV with good diagnostic accuracy (Fig. 1). This is well below the annual ambient radiation exposure from environmental sources. Still, the impact of cumulative radiation from repeated scans over time still deserves consideration and alternatives should be used whenever possible. However, the risk of missing a complication or the risk of not having the needed information to determine appropriate therapy is also real. Therefore, in settings wherein MRI technology is not available or not practical, CTE is a valuable tool.
(Enlarge Image)
Figure 1.
Two coronal reformatted images in a patient with Crohn's disease show active inflammatory stricture in a jejunal bowel segment (arrow) and adjacent small abscess (arrowhead). The examination was performed with reduced dose technique (total estimated radiation dose of 1.3 mSv) and the images were reconstructed utilizing a newly available image reconstruction algorithm to reduce the noise typically associated with the low dose technique. The images show good diagnostic accuracy for identifying the inflamed bowel segment, stricture formation and abscess.
MRI techniques are based on the energy emitted when protons are released from alignment after application of radio frequency pulses in a high-strength magnetic field. Scanners are 'tuned' to evaluate T1 and T2 relaxation times generating weighted images that highlight fat and water, two key bodily substances. T2 weighted images help evaluate for bowel wall thickening and edema. Gadolinium-enhanced T1 weighted images are used to assess the bowel wall enhancement characteristics and to visualize the surrounding vasculature and tissues. The MRI scanning protocols consist of various combinations of sequences that highlight different aspects of the tissue to accomplish different goals. The technical aspects including a review of pathologic findings have been detailed in a recent two-part review by Sinha et al.
The small intestine provides unique challenges for MRI including uneven bowel distention, inconsistent mucosal and bowel wall contrast, and intestinal motility. These challenges have been addressed by specific protocols and sequences. Biphasic oral contrast agents such as VoLumen, a non-absorbable oral contrast that can help evenly distend the small bowel lumen, enable evaluation of the bowel wall demonstrating low T1 and high T2 signal intensity that reproduce water intensity while more evenly distending the bowel, particularly the distal bowel. These agents allow assessment of mucosal enhancement on T1 weighted images, and on T2 weighted images create high contrast between the wall (low T2 signal) and the lumen (high T2 signal) enabling sensitive assessment of fold and wall thickness. The deleterious effects of random bowel motility on MRI image quality, effects that are not improved by breath holding or gaiting as is done for respiratory or cardiac motion compensation, are partially controlled by the use of antiperistaltic agents such as intravenous glucagon or similar agents administered during the sequence acquisition. Finally, application of fat suppression highlights tissue edema on the T2 weighted images. Just like CTE, enhancement and hypervascularity on MRE identify bowel regions with histologic inflammation. Identification of involved bowel regions is indicated by increased mucosal enhancement, wall thickening and stratification, along with mesenteric findings on T1 and T2 weighted images. Like CTE, MRE is sensitive to inflammation, but a recent carefully done histologic study failed to demonstrate specific MRI findings that correlated with fibrosis. As with CTE, the factor most closely correlated with tissue fibrosis was tissue inflammation confirming that the two are closely linked pathologically.
Several recent studies add important information to our understanding of MRE as a tool to assess disease severity and identify complications of Crohn's disease. Fiorino et al. showed that CTE and MRE similarly identify disease localization, wall thickening, bowel wall enhancement (with MRE being slightly more sensitivity for ileal wall enhancement than CTE), fistulae and mesenteric adenopathy. In this study, stricture identification was significantly more sensitive with MRE than CTE. Sensitivities and specificities of MRE for small intestinal findings in Crohn's disease were similar to other reported studies with 0.88 [0.78–0.99, confidence interval (CI) 95%] sensitivity and 0.88 (0.68–1.0, CI 95%) specificity for localization of disease, bowel wall thickening, and bowel wall enhancement. Identification of enteroenteric fistulas was broadly similar between CTE and MRE (0.04 vs. 0.02; P = 0.08, respectively). The study concluded that both CTE and MRE are highly effective techniques in assessing ileocolonic Crohn's disease with broadly similar accuracy.
Under optimal patient circumstances, image quality of MRE rivals CTE. However, in a recent study comparing the two modalities, the image quality of CTE was found to be superior to MRE. Interobserver and intermodality agreement between CTE and MRE was found to be high for both scans. For disease evaluation, the interobserver agreement was high for CTE and moderate for MRE. On the contrary, the intermodality agreement was fair to substantial depending on the reader. This suggests that the evaluation of small bowel Crohn's disease is both observer and modality dependent. However, despite these differences, both techniques had comparable diagnostic yields. Therefore, given an experienced radiologist, both MRE and CTE are comparable alternatives for assessing Crohn's disease.
Compared with CTE, MRE is more expensive, takes longer to perform due to multiple sequence acquisitions compared to the single acquisition in CT and fewer radiologists are trained or feel comfortable reading MRI scans. Further, although variations in CTE protocols exist, CTE protocols are much more standardized between institutions and more easily applied and interpreted in community practice. Therefore, MRE has been slow to gain use beyond major medical centers. As MRI technology becomes more widely applied to the abdomen, MRE will likely become more commonplace, just as CTE is replacing standard abdomen and pelvis CT for imaging the small intestine.
The ability of CTE to detect fibrosis or distinguish between inflammation and fibrosis is not well established. This is an area of enormous clinical importance because the presence of a predominately fibrotic stricture would direct a patient toward surgical therapy rather than continued medical therapy. Some gastroenterologists and radiologists are quick to equate mural thickening without enhancement to fibrostenotic disease. However, caution should be used in equating lack of mural enhancement with fibrosis. Our experience is that very few, if any, surgical samples have only fibrosis; the best predictor of fibrosis is the presence of inflammation. Inflammation and fibrosis seems so closely linked pathologically that we agree with Zappa et al. who found that fibrosis correlated well with inflammation and that the two are inseparable and that 'it may not be relevant to make an exclusive distinction, as is usually done, between inflammatory patients and fibrotic patients'.
Most studies of CTE and MRE evaluate the ability of these techniques to detect inflamed bowel wall regions. Determining the severity of inflammation is less straightforward. The ability to determine severity of inflammation is complex and includes an inflammatory component at each point and the length of involvement, as well as involvement of the thickness of the bowel wall. Recently, Rimola et al. using ileocolonoscopy-derived Crohn's Disease Endoscopic Index of Severity have developed a MRI Index of Activity with elements that correlated with the endoscopic gold standard. A more extensive scoring system that incorporates clinical, endoscopic, and imaging parameters is being considered for a future study.
An imaging parameter being explored for assessment of inflammation, diffusion-weighted imaging (DWI), reflects the changes in the water mobility caused by interactions with cell membranes, macromolecules, and alterations of the tissue environment. DWI is sensitive to molecular diffusion based on the Brownian motion of the spins in biological tissues. This technique has been widely used for intracranial disease, and has shown promise in the abdomen for evaluation of various hepatic, renal, and pancreatic diseases. DWI is now being explored for the evaluation of Crohn's disease. DWI provides information that complements T1/T2 weighted images demonstrating hyperintense signal or restricted diffusion in involved bowel segments. As a diffusion sequence is part of a routine MRI at many centers, one may notice results of diffusion sequences being reported even before the full significance in Crohn's disease has been determined. Hopefully, the rapidly emerging data in this field will shed some light on the significance of these findings.
Advanced sequences like dynamic contrast-enhanced MRI have emerged from the oncology world and are based on sensitivity to altered blood flow. Several studies have addressed the timing of the scan in relation to the injection of gadolinium contrast and its ability to describe tissue inflammation. Dynamic contrast-enhanced MRI quantitatively assesses pharmacokinetic models that correlate with angiogenesis, an important pathologic consequence of chronic inflammation. The qualitative and quantitative analysis of time-signal intensity curves obtained with dynamic contrast-enhanced MRI can help differentiate active vs. inactive Crohn's disease. However, detailed histologic correlation studies on more than a handful of patients are lacking. Dynamic contrast-enhanced MRI requires specifically timed contrast administration and is not likely to become part of our routine scan protocols in the near future.
Magnetization transfer imaging in MRI is being explored as the only MRI sequence shown to correlate specifically with fibrosis. Magnetization transfer takes advantage of a different set of molecular properties than standard T1 and T2 imaging. Magnetization transfer reflects the energy transferred from protons in free mobile water molecules to protons in water molecules associated with large molecules such as collagen. Therefore, stiff body substances such as muscle or fibrotic tissue have a high magnetization transfer effect, whereas magnetization transfer is relatively insensitive to inflammation and tissue edema. Our group has demonstrated that magnetization transfer ratio can semi-quantitatively detect collagen in an animal model of Crohn's disease. Further, the technique is sensitive to the development of fibrosis over time and with treatment.
High-resolution transducers and methods such as measurement of flow parameters in the superior mesenteric artery and contrast enhancement have increased the ability of surface ultrasound to visualize inflamed small and large bowel. Advantages over other cross-sectional imaging techniques include the opportunity for bedside/office performance, lower cost, and lack of ionizing radiation, all of which have driven the increased use of ultrasound for assessment of inflammatory bowel disease, particularly in European centers. A recent study applied intravenous contrast-enhanced ultrasound to distinguish inflammatory vs. fibrotic stenosis in the distal small bowel. Using clinical assessment of stenosis type, contrast-enhanced ultrasound was not able to distinguish between inflammatory and fibrotic strictures. They found that the ultrasound-determined bowel wall vascularity did not improve the diagnostic power of the examination. Ultrasound elastography imaging (UEI) is a promising approach that measures tissue strain in response to an applied force that indirectly reflects fibrosis. This technique has been applied to evaluate chronicity of deep venous thrombosis, degree of fibrosis in hepatic cirrhosis, and kidney rejection after transplantation. UEI has been applied to Crohn's disease where it has shown promise in animal models. The technique has promise for distinguishing inflamed vs. fibrotic strictures.
PET using fluorine-18-labeled-fluoro-2-deoxy-D-glucose (FDG) is a functional imaging method that is sensitive to glucose metabolism. FDG accumulates in areas of active inflammation due to leukocyte overexpression of glucose transporters, and increased metabolic activity. PET can identify inflamed areas of the large and small bowel and can be combined with MR or CT for localization of disease activity. Like MRI techniques and ultrasound methods, PET warrants consideration as an objective, noninvasive, quantifiable method for assessing Crohn's disease activity potentially serving as an endpoint for clinical trials, allowing differentiation between inflammatory and fibrotic strictures, and perhaps allowing for screening for inflammatory pathway cancers. A recent study investigated the diagnostic value of PET CT to determine whether PET added value to the standard CTE. The investigators found no additional inflamed segments beyond the ones identified by CTE. Interestingly, low FDG uptake in an abnormal bowel segment correlated with failure of medical therapy. Although pathologic correlation was lacking, the authors of the study speculated that these segments indicated fibrostenotic disease. Whether the information derived from PET imaging justifies the approximately 4 mSV additional radiation exposure related to the radiolabeled probe requires additional investigation.
Imaging Techniques
Multiple imaging modalities are available for assessing the intestinal tract; each has strengths and weaknesses and often the tests are complementary. Endoscopy-based techniques such as colonoscopy, deep small intestinal endoscopy, and capsule endoscopy are highly sensitive, but only assess the superficial mucosal layers. Cross-sectional imaging is best for visualizing the deep layers of the gut and assessing for strictures, as well as extraluminal complications such as fistulae and abscesses. Because of its broad availability and high spatial resolution, computed tomography (CT) based imaging, especially CT enterography (CTE), has become the most widely used cross-sectional imaging technology for Crohn's disease. Intrinsic to CT technology is the radiation utilized to generate the images. Growing concern about the potential risks associated with cumulative diagnostic radiation exposure, particularly in young patients, has led to growing interest and research into new techniques to minimize radiation from diagnostic CT while maintaining diagnostic quality as well as interest in alternative imaging modalities. At the same time, improved spatial resolution of magnetic resonance (MR) based techniques, along with development of faster imaging sequences have helped overcome bowel motion-related artifacts, and have driven a rapid increase in the use of MR enterography (MRE) for Crohn's imaging. Further, ultrasound offers excellent tissue discrimination with the advantage of being relatively low cost, safe and, potentially, office based. A recent systematic review of the standard imaging modalities applied to Crohn's disease has been published that highlights advances in the field. This review will consider new and future applications of these technologies.
Computed Tomography Enterography
CTE has almost completely replaced the traditional small bowel follow through in most academic centers. The key difference between CTE and standard abdomen and pelvis CT scan lies in the use of low-density oral contrast that results in a low density of the bowel lumen compared with the standard 'white out' of barium or iodine-based oral contrast used for standard scans. In the USA, this is accomplished by the use of FDA-approved VoLumen (Bracco Diagnostics, Westbury, New York, USA) and in European centers by other agents including polyethylene glycol or administration of methylcellulose. CTE also utilizes intravenous iodinated contrast that allows excellent definition of the mucosa revealing enhancement pattern, a highly sensitive indicator of mucosal inflammation. In addition, it helps better delineate the mural stratification and allows for stricture assessment. The use of multidetector CT scanners allows the acquisition of thin axial slices with nearly isotropic voxels which is used to generate high resolution three-dimensional reconstructed images that provide insight into the distribution, nature and significance of inflammation and strictures.
Limiting Radiation
The potential adverse effects of cumulative radiation dosage from diagnostic imaging have gained attention in the medical community and in the lay press. Measurement of effective radiation doses in CT is dependent on several factors, such as scanning technique and patient body habitus. One study by Jaffe et al. found that the mean effective dose for abdominopelvic multidetector CT was 16.1 mSv, which was up to five times higher than small bowel follow through examination. Recently, several changes have been introduced to CT scanning techniques that allow the acquisition of 'low-dose CT', leading to decrease in the overall dose of radiation delivered to the patient undergoing CT examination while maintaining image quality. These changes include the use of automatic tube current modulation (ATCM) and low-voltage (kVp) settings used in the CT scanner along with introduction of new image reconstruction algorithms that reduce the image noise typically associated with these techniques. Dose reduction efforts have resulted in markedly decreased radiation exposure. The most recent algorithms have the potential to reduce radiation exposure from CT scanning below 1 mSV with good diagnostic accuracy (Fig. 1). This is well below the annual ambient radiation exposure from environmental sources. Still, the impact of cumulative radiation from repeated scans over time still deserves consideration and alternatives should be used whenever possible. However, the risk of missing a complication or the risk of not having the needed information to determine appropriate therapy is also real. Therefore, in settings wherein MRI technology is not available or not practical, CTE is a valuable tool.
(Enlarge Image)
Figure 1.
Two coronal reformatted images in a patient with Crohn's disease show active inflammatory stricture in a jejunal bowel segment (arrow) and adjacent small abscess (arrowhead). The examination was performed with reduced dose technique (total estimated radiation dose of 1.3 mSv) and the images were reconstructed utilizing a newly available image reconstruction algorithm to reduce the noise typically associated with the low dose technique. The images show good diagnostic accuracy for identifying the inflamed bowel segment, stricture formation and abscess.
Magnetic Resonance Enterography
MRI techniques are based on the energy emitted when protons are released from alignment after application of radio frequency pulses in a high-strength magnetic field. Scanners are 'tuned' to evaluate T1 and T2 relaxation times generating weighted images that highlight fat and water, two key bodily substances. T2 weighted images help evaluate for bowel wall thickening and edema. Gadolinium-enhanced T1 weighted images are used to assess the bowel wall enhancement characteristics and to visualize the surrounding vasculature and tissues. The MRI scanning protocols consist of various combinations of sequences that highlight different aspects of the tissue to accomplish different goals. The technical aspects including a review of pathologic findings have been detailed in a recent two-part review by Sinha et al.
The small intestine provides unique challenges for MRI including uneven bowel distention, inconsistent mucosal and bowel wall contrast, and intestinal motility. These challenges have been addressed by specific protocols and sequences. Biphasic oral contrast agents such as VoLumen, a non-absorbable oral contrast that can help evenly distend the small bowel lumen, enable evaluation of the bowel wall demonstrating low T1 and high T2 signal intensity that reproduce water intensity while more evenly distending the bowel, particularly the distal bowel. These agents allow assessment of mucosal enhancement on T1 weighted images, and on T2 weighted images create high contrast between the wall (low T2 signal) and the lumen (high T2 signal) enabling sensitive assessment of fold and wall thickness. The deleterious effects of random bowel motility on MRI image quality, effects that are not improved by breath holding or gaiting as is done for respiratory or cardiac motion compensation, are partially controlled by the use of antiperistaltic agents such as intravenous glucagon or similar agents administered during the sequence acquisition. Finally, application of fat suppression highlights tissue edema on the T2 weighted images. Just like CTE, enhancement and hypervascularity on MRE identify bowel regions with histologic inflammation. Identification of involved bowel regions is indicated by increased mucosal enhancement, wall thickening and stratification, along with mesenteric findings on T1 and T2 weighted images. Like CTE, MRE is sensitive to inflammation, but a recent carefully done histologic study failed to demonstrate specific MRI findings that correlated with fibrosis. As with CTE, the factor most closely correlated with tissue fibrosis was tissue inflammation confirming that the two are closely linked pathologically.
Performance Characteristics of Computed Tomography Enterography and Magnetic Resonance Enterography
Several recent studies add important information to our understanding of MRE as a tool to assess disease severity and identify complications of Crohn's disease. Fiorino et al. showed that CTE and MRE similarly identify disease localization, wall thickening, bowel wall enhancement (with MRE being slightly more sensitivity for ileal wall enhancement than CTE), fistulae and mesenteric adenopathy. In this study, stricture identification was significantly more sensitive with MRE than CTE. Sensitivities and specificities of MRE for small intestinal findings in Crohn's disease were similar to other reported studies with 0.88 [0.78–0.99, confidence interval (CI) 95%] sensitivity and 0.88 (0.68–1.0, CI 95%) specificity for localization of disease, bowel wall thickening, and bowel wall enhancement. Identification of enteroenteric fistulas was broadly similar between CTE and MRE (0.04 vs. 0.02; P = 0.08, respectively). The study concluded that both CTE and MRE are highly effective techniques in assessing ileocolonic Crohn's disease with broadly similar accuracy.
Under optimal patient circumstances, image quality of MRE rivals CTE. However, in a recent study comparing the two modalities, the image quality of CTE was found to be superior to MRE. Interobserver and intermodality agreement between CTE and MRE was found to be high for both scans. For disease evaluation, the interobserver agreement was high for CTE and moderate for MRE. On the contrary, the intermodality agreement was fair to substantial depending on the reader. This suggests that the evaluation of small bowel Crohn's disease is both observer and modality dependent. However, despite these differences, both techniques had comparable diagnostic yields. Therefore, given an experienced radiologist, both MRE and CTE are comparable alternatives for assessing Crohn's disease.
Compared with CTE, MRE is more expensive, takes longer to perform due to multiple sequence acquisitions compared to the single acquisition in CT and fewer radiologists are trained or feel comfortable reading MRI scans. Further, although variations in CTE protocols exist, CTE protocols are much more standardized between institutions and more easily applied and interpreted in community practice. Therefore, MRE has been slow to gain use beyond major medical centers. As MRI technology becomes more widely applied to the abdomen, MRE will likely become more commonplace, just as CTE is replacing standard abdomen and pelvis CT for imaging the small intestine.
Distinguishing Inflammation from Fibrosis
The ability of CTE to detect fibrosis or distinguish between inflammation and fibrosis is not well established. This is an area of enormous clinical importance because the presence of a predominately fibrotic stricture would direct a patient toward surgical therapy rather than continued medical therapy. Some gastroenterologists and radiologists are quick to equate mural thickening without enhancement to fibrostenotic disease. However, caution should be used in equating lack of mural enhancement with fibrosis. Our experience is that very few, if any, surgical samples have only fibrosis; the best predictor of fibrosis is the presence of inflammation. Inflammation and fibrosis seems so closely linked pathologically that we agree with Zappa et al. who found that fibrosis correlated well with inflammation and that the two are inseparable and that 'it may not be relevant to make an exclusive distinction, as is usually done, between inflammatory patients and fibrotic patients'.
Special MRI Sequences
Most studies of CTE and MRE evaluate the ability of these techniques to detect inflamed bowel wall regions. Determining the severity of inflammation is less straightforward. The ability to determine severity of inflammation is complex and includes an inflammatory component at each point and the length of involvement, as well as involvement of the thickness of the bowel wall. Recently, Rimola et al. using ileocolonoscopy-derived Crohn's Disease Endoscopic Index of Severity have developed a MRI Index of Activity with elements that correlated with the endoscopic gold standard. A more extensive scoring system that incorporates clinical, endoscopic, and imaging parameters is being considered for a future study.
An imaging parameter being explored for assessment of inflammation, diffusion-weighted imaging (DWI), reflects the changes in the water mobility caused by interactions with cell membranes, macromolecules, and alterations of the tissue environment. DWI is sensitive to molecular diffusion based on the Brownian motion of the spins in biological tissues. This technique has been widely used for intracranial disease, and has shown promise in the abdomen for evaluation of various hepatic, renal, and pancreatic diseases. DWI is now being explored for the evaluation of Crohn's disease. DWI provides information that complements T1/T2 weighted images demonstrating hyperintense signal or restricted diffusion in involved bowel segments. As a diffusion sequence is part of a routine MRI at many centers, one may notice results of diffusion sequences being reported even before the full significance in Crohn's disease has been determined. Hopefully, the rapidly emerging data in this field will shed some light on the significance of these findings.
Advanced sequences like dynamic contrast-enhanced MRI have emerged from the oncology world and are based on sensitivity to altered blood flow. Several studies have addressed the timing of the scan in relation to the injection of gadolinium contrast and its ability to describe tissue inflammation. Dynamic contrast-enhanced MRI quantitatively assesses pharmacokinetic models that correlate with angiogenesis, an important pathologic consequence of chronic inflammation. The qualitative and quantitative analysis of time-signal intensity curves obtained with dynamic contrast-enhanced MRI can help differentiate active vs. inactive Crohn's disease. However, detailed histologic correlation studies on more than a handful of patients are lacking. Dynamic contrast-enhanced MRI requires specifically timed contrast administration and is not likely to become part of our routine scan protocols in the near future.
Magnetization transfer imaging in MRI is being explored as the only MRI sequence shown to correlate specifically with fibrosis. Magnetization transfer takes advantage of a different set of molecular properties than standard T1 and T2 imaging. Magnetization transfer reflects the energy transferred from protons in free mobile water molecules to protons in water molecules associated with large molecules such as collagen. Therefore, stiff body substances such as muscle or fibrotic tissue have a high magnetization transfer effect, whereas magnetization transfer is relatively insensitive to inflammation and tissue edema. Our group has demonstrated that magnetization transfer ratio can semi-quantitatively detect collagen in an animal model of Crohn's disease. Further, the technique is sensitive to the development of fibrosis over time and with treatment.
Surface Ultrasound and Ultrasound Elastography
High-resolution transducers and methods such as measurement of flow parameters in the superior mesenteric artery and contrast enhancement have increased the ability of surface ultrasound to visualize inflamed small and large bowel. Advantages over other cross-sectional imaging techniques include the opportunity for bedside/office performance, lower cost, and lack of ionizing radiation, all of which have driven the increased use of ultrasound for assessment of inflammatory bowel disease, particularly in European centers. A recent study applied intravenous contrast-enhanced ultrasound to distinguish inflammatory vs. fibrotic stenosis in the distal small bowel. Using clinical assessment of stenosis type, contrast-enhanced ultrasound was not able to distinguish between inflammatory and fibrotic strictures. They found that the ultrasound-determined bowel wall vascularity did not improve the diagnostic power of the examination. Ultrasound elastography imaging (UEI) is a promising approach that measures tissue strain in response to an applied force that indirectly reflects fibrosis. This technique has been applied to evaluate chronicity of deep venous thrombosis, degree of fibrosis in hepatic cirrhosis, and kidney rejection after transplantation. UEI has been applied to Crohn's disease where it has shown promise in animal models. The technique has promise for distinguishing inflamed vs. fibrotic strictures.
PET Sequences
PET using fluorine-18-labeled-fluoro-2-deoxy-D-glucose (FDG) is a functional imaging method that is sensitive to glucose metabolism. FDG accumulates in areas of active inflammation due to leukocyte overexpression of glucose transporters, and increased metabolic activity. PET can identify inflamed areas of the large and small bowel and can be combined with MR or CT for localization of disease activity. Like MRI techniques and ultrasound methods, PET warrants consideration as an objective, noninvasive, quantifiable method for assessing Crohn's disease activity potentially serving as an endpoint for clinical trials, allowing differentiation between inflammatory and fibrotic strictures, and perhaps allowing for screening for inflammatory pathway cancers. A recent study investigated the diagnostic value of PET CT to determine whether PET added value to the standard CTE. The investigators found no additional inflamed segments beyond the ones identified by CTE. Interestingly, low FDG uptake in an abnormal bowel segment correlated with failure of medical therapy. Although pathologic correlation was lacking, the authors of the study speculated that these segments indicated fibrostenotic disease. Whether the information derived from PET imaging justifies the approximately 4 mSV additional radiation exposure related to the radiolabeled probe requires additional investigation.
