Radiogenomic imaging-linking diagnostic imaging and molecular diagnostics.

Radiogenomic imaging refers to the correlation between cancer imaging features and gene expression and is one of the most promising areas within science and medicine. High-throughput biological techniques have reshaped the perspective of biomedical research allowing for fast and efficient assessment of the entire molecular topography of a cell's physiology providing new insights into human cancers. The use of non-invasive imaging tools for gene expression profiling of solid tumors could serve as a means for linking specific imaging features with specific gene expression patterns thereby allowing for more accurate diagnosis and prognosis and obviating the need for high-risk invasive biopsy procedures. This review focuses on the medical imaging part as one of the main drivers for the development of radiogenomic imaging.

Healthcare costs for new technologies.

INTRODUCTION: Continuous ageing of the population coupled with growing health consciousness and continuous technological advances have fueled the rapid rise in healthcare costs in the United States and Europe for the past several decades. The exact impact of new medical technology on long-term spending growth remains the subject of controversy. By all measures it is apparent that new medical technology is the dominant driver of increases in health-care costs and hence insurance premiums. OBJECTIVE: This paper addresses the impact of medical technology on healthcare delivery systems with regard to medical practice and costs. We first explore factors affecting the growth of medical technology and then attempt to provide a means for assessing the effectiveness of medical technology. DISCUSSION: Avoidable healthcare cost drivers are identified and related policy issues are discussed.

Gadofosveset-enhanced magnetic resonance angiography.

Gadofosveset (Vasovist, Bayer Schering Pharma AG, Berlin/Germany) is the first intravascular contrast agent approved for use with magnetic resonance angiography in the European Union, Switzerland, Turkey, Canada, and Australia. Gadofosveset reversibly binds to albumin providing extended intravascular enhancement compared wth existing extracellular magnetic resonance contrast agents. Prior to approval, gadofosveset underwent extensive testing to evaluate the safety and efficacy of the drug; the clinical trials show that gadofosveset-enhanced magnetic resonance angiography (MRA) is safe and well tolerated in patients with vascular disease and effective for the detection of vascular stenosis and aneurysms gadofosveset has the potential to open new horizons in diagnostic MRA by increasing the spatial resolution and the robustness of MRA examinations and facilitating the examination of multiple vascular beds.

Recent advances in contrast-enhanced magnetic resonance angiography.

Magnetic resonance angiography (MRA) provides a means of visualizing vascular structures noninvasively and is increasingly replacing conventional X-ray angiography in routine use. Contrast-enhanced MRA (CE-MRA), in which gadolinium contrast agents are used to shorten the T1 relaxation, offers increased resolution and higher signal-to-noise ratio compared with earlier flow-dependent [time-of-flight (TOF) or phase-contrast (PC)] techniques. Currently available contrast agents differ in their ability to lower T1 values, and hence the choice of contrast agent is an important consideration in the successful use of CE-MRA. Gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany) is the first of a new class of intravascular contrast agents. This agent is extensively (approximately 85%) and reversibly bound to human serum albumin and is retained within the vasculature thus allowing steady-state imaging to be perform-ed. An additional benefit is that gadofosveset offers higher relaxivity compared with other contrast agents, thus giving a lower blood T1 values which also makes it ideal for first-pass imaging. Clinical trials have consistently shown that gadofosveset enhanced MRA is more sensitive, specific and accurate than time-of-flight MRA, gives fewer uninterpretable scans and affords greater diagnostic confidence. Intravascular contrast agents such as gadofosveset, therefore, offer the potential for improved vascular imaging.

Magnetic resonance angiography with blood-pool contrast agents: future applications.

Blood pool agents remain in the intravascular space for a longer time period. Therefore the optimal imaging window for vascular structures is widened to about 30 minutes. Gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany) is the first blood-pool contrast agent approved in Europe for contrast-enhanced magnetic resonance angiography (MRA) of vessels in the abdomen, pelvis and lower extremity in adults. Other possible applications of blood-pool agents are now being considered, such as assessment of venous thromboembolism, coronary artery disease or sinus venous thrombosis. Perfusion MR imaging holds promise for detecting lung perfusion defects with higher spatial resolution and reduced scan time compared with radionuclide scintigraphy. In coronary artery disease, blood-pool agents enable a substantial increase in the quality of coronary artery imaging. Quantitative myocardial perfusion and myocardial viability seem to be possible, although modifications in protocols and sequence design are necessary for optimal results. Other novel applications of blood-pool agents include monitoring of inflammatory changes in systemic lupus erythematosus and evaluation of tumour invasion into lymph nodes and more reliable assessment of cerebral venous and sinus thombosis.

Utility of dark-lumen MR colonography for the assessment of extra-colonic organs.

The aim of the study was to evaluate the utility of dark-lumen MR colonography (MRC) for the assessment of extra-colonic organs. Three hundred seventy-five subjects with suspected colonic disease underwent a complete MRC examination. MRC data were evaluated by two radiologists in a blinded fashion. In addition to the large bowel, the extra-intestinal organs from the lung bases to the pelvis were assessed for the presence of pathologies. All findings were divided into known or unknown findings and therapeutically relevant or irrelevant findings. If deemed necessary, other diagnostic imaging tests to further assess those findings were performed. In total, 510 extra-colonic findings were found in 260 (69%) of the 375 subjects. Known extra-colonic findings were found in 140 subjects (54%) and unknown findings in 120 subjects (46%). Thirty-one (12%) of the 260 subjects had therapeutically relevant findings (45 findings); 229 patients (88%) had irrelevant findings (465 findings). Dark-lumen MRC is a useful tool not only for the assessment of the entire colon, but also for the evaluation of extra-colonic organs. Thus, intra- and extra-colonic pathologies can be diagnosed within the same examination.

A multicenter, site-independent, blinded study to compare the diagnostic accuracy of contrast-enhanced magnetic resonance angiography using 1.0M gadobutrol (Gadovist) to intraarterial digital subtraction angiography in body arteries.

PURPOSE: Prospective evaluation of diagnostic accuracy of single field-of-view contrast-enhanced MR Angiography (ceMRA) with 1.0M gadobutrol compared to intraarterial DSA in body arteries. MATERIALS AND METHODS: In an European multicenter study 179 patients underwent ceMRA and DSA. For each indication five prospectively defined vessel segments were evaluated by local investigators onsite and by three site-independent blinded readers (BR) independently. RESULTS: The agreement between ceMRA and DSA diagnosis was statistically significant in the onsite (96.6%) and blinded reader (86.6-90.2%) evaluation. Sensitivity, specificity, accuracy, positive (PPV) and negative predictive values (NPV) for detection of relevant stenosis (>50%) were calculated for the right and left internal carotid arteries, and common and external iliac arteries: Sensitivity was 95-98% (onsite) and 76-96% (BR), specificity 94-96% (onsite) and 86-94% (BR), accuracy 96% (onsite) and 87-93% (BR), NPV 98-99% (onsite) and 84-98% (BR), and PPV 79-93% (onsite) and 44-91% (BR), respectively. CONCLUSION: CeMRA of body arteries using 1.0M gadobutrol provides diagnostic information comparable to intraarterial DSA.

MR imaging of the colon: "technique, indications, results and limitations".

In the last few years virtual colonography using MR imaging has shown a proceeding development regarding detection and quantification of colorectal pathologies. Dark-lumen MR colonography (MRC) has been a leading tool for the diagnosis of the entire colon and their pathologies. This review article describes some of the underlying techniques of MRC concerning data acquisition, the need for intravenously applied paramagnetic contrast agent, as well as indications, results and limitations of MRC for the detection of colorectal pathologies. In addition, new techniques to improve patient acceptance are discussed.

Gadofosveset: the first intravascular contrast agent EU-approved for use with magnetic resonance angiography.

Gadofosveset is the first intravascular contrast agent approved for use with magnetic resonance angiography in the European Union. Gadofosveset reversibly binds to albumin, providing extended intravascular enhancement beyond that of existing extracellular magnetic resonance contrast agents. Prior to approval, gadofosveset underwent extensive testing to evaluate the safety and efficacy of the drug; the clinical trials program included blinded, placebo-controlled, dose-ranging, efficacy in a variety of vascular beds (areas of turbulent blood flow, renal and pedal), examination of potential drug interaction with warfarin and comparison with x-ray angiography. The clinical trials demonstrate that gadofosveset-enhanced magentic resonance angiography is: safe and well tolerated in patients with vascular disease; effective for the detection of vascular stenosis and aneurysms; significantly more accurate (both more sensitive and specific) than noncontrast magnetic resonance angiography for the diagnosis of vascular stenoses; and similar to conventional angiography for the overall characterization of vascular disease, without the need for catheterization.

Strengths and weaknesses of dark-lumen MR colonography: clinical relevance of polyps smaller than 5 mm in diameter at the moment of their detection.

PURPOSE: To assess the clinical relevance of dark-lumen MR colonography (MRC) for the detection of colorectal lesions using conventional colonoscopy (CC) and histopathologic examinations as reference standard. MATERIALS AND METHODS: A total of 72 patients underwent MRC and CC. MRC was performed using a contrast-enhanced high spatial resolution T1 weighted 3D volumetric interpolated breathhold examination (VIBE)-sequence. All removed colorectal lesions were evaluated by an experienced pathologist. RESULTS: CC confirmed 65 polyps less than 5 mm in diameter. Non of those lesions could be detected using MRC. Just two (4%) of the 49 removed lesions smaller than 5 mm showed signs of dysplasia. Additionally, CC confirmed 25 polyps between 6-15 mm in diameter (MRC 22). All those 25 lesions were removed in CC. Only four (16%) of those polyps showed signs of dysplasia and malignancy (11, 13, 13 and 15 mm). CONCLUSION: Dark-lumen MRC failed to detect all polyps smaller than 5 mm in diameter which are generally not clinically relevant at the moment of their detection and thus can be kept under surveillance. However, MRC as a non-invasive imaging modality is a promising alternative to CC in the detection of clinically relevant polyps larger than 5 mm in diameter.

MR colonography for the assessment of colonic anastomoses.

PURPOSE: To assess colonic anastomoses in patients after surgical treatment by means of MR colonography (MRC) in comparison with conventional colonoscopy (CC). MATERIALS AND METHODS: A total of 39 patients who had previously undergone colonic resection and end-to-end-anastomosis were included in the study. MRI was based on a dark-lumen approach. Contrast-enhanced T1-weighted (T1w) three-dimensional (3D) images were collected following the rectal administration of water for colonic distension. The MRC data were evaluated by two radiologists. The criteria employed to evaluate the anastomoses included bowel wall thickening and increased contrast uptake in this region. Furthermore, all other colonic segments were assessed for the presence of pathologies. RESULTS: In 23 and 20 patients the anastomosis was rated to be normal by MRC and CC, respectively. In three patients CC revealed a slight inflammation of the anastomosis that was missed by MRI. A moderate stenosis of the anastomosis without inflammation was detected by MRC in five patients, which was confirmed by CC. In the remaining 11 patients a relevant pathology of the anastomosis was diagnosed by both MRC and CC. Recurrent tumor was diagnosed in two patients with a history of colorectal carcinoma. In the other nine patients inflammation of the anastomosis was seen in seven with Crohn's disease (CD) and two with ulcerative colitis. MRC did not yield any false-positive findings, resulting in an overall sensitivity/specificity for the assessment of the anastomosis of 84%/100%. CONCLUSION: MRC represents a promising alternative to CC for the assessment of colonic anastomoses in patients with previous colonic resection.

Vasovist-enhanced MR angiography.

Vasovist (MS-325) is the first intravascular contrast agent approved for use with magnetic resonance angiography in the European Union. Vasovist reversibly binds to albumin, providing extended intravascular enhancement compared to existing extracellular magnetic resonance contrast agents. Prior to approval, Vasovist underwent extensive testing to evaluate the safety and efficacy of the drug; the clinical trials program included blinded, placebo-controlled dose ranging, efficacy in a variety of vascular beds (AIOD, renal, pedal), examination of potential drug interaction with warfarin and comparison with XRA. The clinical trials show that Vasovist-enhanced MR angiography is safe and well-tolerated in patients with vascular disease, effective for the detection of vascular stenosis and aneurysms, significantly more accurate (both more sensitive and specific) than non-contrast MR angiography for the diagnosis of vascular stenoses, and similar to conventional angiography for the overall characterization of vascular disease, without the need for catheterization.

Total-body 3D magnetic resonance angiography influences the management of patients with peripheral arterial occlusive disease.

High-resolution total-body 3D MR angiography (MRA) has recently become available, revealing additional clinically relevant disease in patients with peripheral arterial occlusive disease (PAOD). However, the actual impact of total-body MRA on patient management in patients with PAOD has not been investigated so far. Two hundred forty-nine consecutive patients with angiographically proven PAOD were prospectively examined by means of contrast-enhanced total-body 3D MRA on a 1.5-T MR scanner. All correlative imaging studies performed within 60 days of total-body MRA were included in the efficacy analysis. Additional clinically relevant disease (luminal narrowing >50%, aneurysmal changes or dissections) was found in 73 segments (52 patients), including the renal arteries (36 segments), carotid arteries (28 segments), subclavian arteries (four segments) and abdominal aortic aneurysms (AAA) (five segments). Of the 73 segments, 36 were deemed necessary for further investigation by means of focused MRA examinations; the diagnosis was confirmed in all cases. Within the 60-day follow-up period, interventional or surgical therapy outside the peripheral arterial tree was performed in nine patients (11 segments), including carotid endatherectomy and renal artery angioplasty. The outlined total-body 3D MRA approach permits a comprehensive evaluation of the arterial system in patients with atherosclerosis and does indeed have an impact on patient management in patients with PAOD.

Dark-lumen magnetic resonance colonography in patients with suspected sigmoid diverticulitis: a feasibility study.

To assess dark-lumen magnetic resonance colonography (MRC) for the evaluation of patients with suspected sigmoid diverticulitis. Forty patients with suspected sigmoid diverticulitis underwent MRC within 72 h prior to conventional colonoscopy (CC). A three-dimensional T1-weighted volumetric interpolated breath-hold examination sequence was acquired after an aqueous enema and intravenous administration of gadolinium-based contrast agents. All MRC data were evaluated by two radiologists. Based on wall thickness and focal uptake of contrast material and pericolic reaction including mesenteric infiltration on T1-weighted sequence the sigmoid colon was assessed for the presence of diverticulitis. MRC classified 17 of the 40 patients as normal with regard to sigmoid diverticulitis. However, CC confirmed the presence of light inflammatory signs in four patients which were missed in MRC. MRC correctly identified wall thickness and contrast uptake of the sigmoid colon in the other 23 patients. In three of these patients false-positive findings were observed, and MRC classified the inflammation of the sigmoid colon as diverticulitis whereas CC and histopathology confirmed invasive carcinoma. MRC detected additionally relevant pathologies of the entire colon and could be performed in cases where CC was incomplete. MRC may be considered a promising alternative to CC for the detection of sigmoid diverticulitis.

Elective full-body screening examinations: a plea for MRI.

The use of imaging is generally focussed on detecting and characterising suspected or known disease in symptomatic patients. Experience with preventative imaging, aiming at the detection of disease prior to its symptomatic manifestation, is limited. Screening involves the evaluation of asymptomatic individuals at risk for the presence of a particular disease. A screening test is designed to detect a targeted disease at a stage which still permits treatment to succeed in avoiding morbidity and/or mortality. Diseases worthy of screening should be associated with high morbidity and/or mortality if proper treatment is not applied sufficiently early. The screening test itself must not cause harm to the examined subjects. For the test to be cost-effective, the target disease should be highly prevalent in the screened population. Restricting screening to a population known to be at increased risk for the target disease enhances the test's effectiveness.

MR angiography of aortoiliac occlusive disease: a phase III study of the safety and effectiveness of the blood-pool contrast agent MS-325.

PURPOSE: To evaluate prospectively the safety and effectiveness of aortoiliac magnetic resonance (MR) angiography enhanced with MS-325 (gadofosveset trisodium) at a dose of 0.03 mmol/kg; effectiveness was defined as accuracy relative to the reference standard, conventional angiography. MATERIALS AND METHODS: Study was approved by institutional review boards of participating institutions, and required national approvals were obtained. Study protocol conformed to Good Clinical Practice guidelines, and informed patient consent was obtained. Patients with known or suspected peripheral vascular disease received 0.03 mmol/kg MS-325 for aortoiliac MR angiography. They were also examined with conventional angiography. MS-325-enhanced MR was evaluated for safety and effectiveness. Along with unenhanced two-dimensional time-of-flight MR angiography, it was compared with conventional angiography for presence of vascular stenosis. Student t tests were used to identify significant improvement in diagnostic sensitivity, specificity, and accuracy, as well as quantitative characterization of stenoses by three blinded readers. Correlations between readers of conventional angiograms were calculated and compared with MR results. RESULTS: In 174 patients, MS-325-enhanced MR angiography showed significant improvement (P < or = .001) in sensitivity, specificity, and accuracy for diagnosis of clinically significant (> or =50%) stenosis, compared with unenhanced MR. For all readers, areas under the receiver operating characteristic curve for both quantitative and qualitative measures of significant disease increased (P < .001) for MS-325-enhanced MR compared with time-of-flight MR. All readers also expressed higher confidence in diagnosis (P < .001) and found fewer images uninterpretable with MS-325 enhancement. All measures of interpretation accuracy approached corresponding measures of correlation between readers of conventional angiograms. Incidence of severe and serious adverse events with MS-325 was low. No patients were withdrawn from study due to adverse events or abnormalities in laboratory results. There were no clinically important trends in findings at hematology, blood chemistry, urinalysis, electrocardiography, or physical examination. CONCLUSION: MR angiography with MS-325 provides significant improvement in effectiveness over unenhanced MR (and minimal and transient side effects) at a dose of 0.03 mmol/kg and was safe and effective for MR evaluation of patients with aortoiliac occlusive disease.

Magnetic resonance colonography without bowel cleansing using oral and rectal stool softeners (fecal cracking)--a feasibility study.

The aim of our study was to assess the effect of oral and rectal stool softeners on dark-lumen magnetic resonance (MR) colonography without bowel cleansing. Ten volunteers underwent MR colonography without colonic cleansing. A baseline examination was performed without oral or rectal administration of stool softeners. In a second set, volunteers ingested 60 ml of lactulose 24 h prior to MR examination. In a third examination, water as a rectal enema was replaced by a solution of 0.5%-docusate sodium (DS). A fourth MR examination was performed, in conjunction with both oral administration of lactulose and rectal application of DS. A T1-weighted data set was acquired at scanning times of 0, 5 and 10 min after colonic filling. A fourth data set was acquired 75 s after i.v. injection of contrast agent. Signal intensity of stool was calculated for all colonic segments. Without oral ingestion of lactulose or rectal enema with DS stool signal intensity was high and did not decrease over time. However, lactulose and DS caused a decrease in stool signal intensity. Both substances together led to a decreasing signal intensity of feces. Combination of lactulose and DS provided the lowest signal intensity of stool. Thus, feces could hardly be distinguished from dark rectal enema allowing for the assessment of the colonic wall.