Soft drug inhibitors for the epigenetic targets lysine-specific demethylase 1 and histone deacetylases.

Epigenetic modulators such as lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) are drug targets for cancer, neuropsychiatric disease, or inflammation, but inhibitors of these enzymes exhibit considerable side effects. For a potential local treatment with reduced systemic toxicity, we present here soft drug candidates as new LSD1 and HDAC inhibitors. A soft drug is a compound that is degraded in vivo to less active metabolites after having achieved its therapeutic function. This has been successfully applied for corticosteroids in the clinic, but soft drugs targeting epigenetic enzymes are scarce, with the HDAC inhibitor remetinostat being the only example. We have developed new methyl ester-containing inhibitors targeting LSD1 or HDACs and compared the biological activities of these to their respective carboxylic acid cleavage products. In vitro activity assays, cellular experiments, and a stability assay identified potent HDAC and LSD1 soft drug candidates that are superior to their corresponding carboxylic acids in cellular models.

Structure-Based Design, Docking and Binding Free Energy Calculations of A366 Derivatives as Spindlin1 Inhibitors.

The chromatin reader protein Spindlin1 plays an important role in epigenetic regulation, through which it has been linked to several types of malignant tumors. In the current work, we report on the development of novel analogs of the previously published lead inhibitor A366. In an effort to improve the activity and explore the structure-activity relationship (SAR), a series of 21 derivatives was synthesized, tested in vitro, and investigated by means of molecular modeling tools. Docking studies and molecular dynamics (MD) simulations were performed to analyze and rationalize the structural differences responsible for the Spindlin1 activity. The analysis of MD simulations shed light on the important interactions. Our study highlighted the main structural features that are required for Spindlin1 inhibitory activity, which include a positively charged pyrrolidine moiety embedded into the aromatic cage connected via a propyloxy linker to the 2-aminoindole core. Of the latter, the amidine group anchor the compounds into the pocket through salt bridge interactions with Asp184. Different protocols were tested to identify a fast in silico method that could help to discriminate between active and inactive compounds within the A366 series. Rescoring the docking poses with MM-GBSA calculations was successful in this regard. Because A366 is known to be a G9a inhibitor, the most active developed Spindlin1 inhibitors were also tested over G9a and GLP to verify the selectivity profile of the A366 analogs. This resulted in the discovery of diverse selective compounds, among which 1s and 1t showed Spindlin1 activity in the nanomolar range and selectivity over G9a and GLP. Finally, future design hypotheses were suggested based on our findings.

The effect of tibial slope in acute ACL-insufficient patients on concurrent meniscal tears.

INTRODUCTION: The aim of this study is to evaluate the effect of the medial and lateral posterior tibial slope (MPTS, LPTS) in patients with acutely ruptured ACL on the menisci. It was hypothesized that medial and lateral meniscus lesions are seen more often with high PTS (posterior tibial slope). We hypothesized that in case of a high tibial slope a possible meniscus lesion is more often located in the posterior horn of the meniscus than in knees with a low tibial slope. MATERIALS AND METHODS: We identified 537 patients with ACL insufficiency between 2012 and 2013. Of these, 71 patients were eligible for the study according to the study's criteria. PTS was measured via MRI and classified into two groups: >10° for high tibial slope and ≤10° for low tibial slope. Any meniscal lesion was documented during arthroscopic ACL reconstruction and evaluated regarding meniscal lesion patterns with high and low PTS, taking into account the type and the location of the tear (anterior horn, intermediate part and posterior horn). Statistical analysis for differences in meniscal lesion was performed using Chi-square tests and McNemar tests for dependent variables. The level of significance was set at p ≤ 0.05. RESULTS: High PTS (MPTS and LPTS) was associated with a higher incidence of meniscal lesions with an odds ratio of 2.11, respectively, 3.44; however, no statistical significance was found. Among the total number of ACL-insufficient knees studied, the meniscal lesion spread more often to the posterior part in the group with a low PTS. In contrast, less damage of the posterior horn of the meniscus could be found in the group with a high PTS. CONCLUSION: High PTS seems to predetermine for meniscal lesion in an acute ACL-insufficient knee. More damage to the posterior part of the menisci could generally be seen but was not associated with a high PTS. There was no statistical significance to support the initial hypothesis. Further research is needed to find out if factors other than tibial slope are risk factors for meniscal lesion in acute ACL injury. LEVEL OF EVIDENCE: IV.

Optimized multidetector computed tomographic protocol for the diagnosis of active obscure gastrointestinal bleeding: a feasibility study.

OBJECTIVE: The purpose of this feasibility study was to prospectively evaluate an optimized multidetector computed tomographic protocol for the diagnosis of active obscure gastrointestinal bleeding (OGIB). METHODS: Between October 2006 and February 2008, patients admitted for active OGIB were included in this prospective unicenter study. Water was administered orally and rectally as neutral luminal contrast material. A contrast-enhanced 16-row multidetector computed tomography (MDCT) was performed in the arterial and venous phases. Mesenteric digital subtraction angiography was carried out immediately after MDCT as standard of reference. RESULTS: Six patients were included in this study. Multidetector computed tomography identified the bleeding site and source in 5 (83%) of the patients. Digital subtraction angiography was performed in 4 patients, and the result was positive in 1 (25%) of the patients. Multidetector computed tomography detected the site and source of bleeding in 2 patients whose digital subtraction angiographic result was negative. CONCLUSIONS: The results of this feasibility study indicate that optimized MDCT is an excellent diagnostic tool for the diagnosis of active OGIB.

Clinical and Radiological Regeneration of Large and Deep Osteochondral Defects of the Knee by Bone Augmentation Combined With Matrix-Guided Autologous Chondrocyte Transplantation.

BACKGROUND: Large osteochondral defects of the knee are a challenge for regenerative treatment. While matrix-guided autologous chondrocyte transplantation (MACT) represents a successful treatment for chondral defects, the treatment potential in combination with bone grafting by cancellous bone or bone block augmentation for large and deep osteochondral defects has not been evaluated. PURPOSE: To evaluate 1- to 3-year clinical outcomes and radiological results on magnetic resonance imaging (MRI) after the treatment of large osteochondral defects of the knee with bone augmentation and MACT. Special emphasis is placed on different methods of bone grafting (cancellous bone grafting or bone block augmentation). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Fifty-one patients were included. Five patients were lost to follow-up. This left 46 patients (mean age, 28.2 years) with a median follow-up time of 2 years. The 46 patients had 47 deep, large osteochondral defects of the knee joint (1 patient with bilateral defects; mean defect size, 6.7 cm2). The origin of the osteochondral defects was osteochondritis dissecans (n = 34), osteonecrosis (n = 8), or subchondral cysts (n = 5). Depending on the depth, all defects were treated by cancellous bone grafting (defect depth ≤10 mm; n = 16) or bone block augmentation (defect depth >10 mm; n = 31) combined with MACT. Clinical outcomes were followed at 3 months, 6 months, 1 year, 2 years, and 3 years and evaluated using the International Knee Documentation Committee (IKDC) score and Cincinnati score. A magnetic resonance imaging (MRI) evaluation was performed at 1 and 2 years, and the magnetic resonance observation of cartilage repair tissue (MOCART) score with additional specific subchondral bone parameters (bone regeneration, bone signal quality, osteophytes, sclerotic areas, and edema) was analyzed. RESULTS: The clinical outcome scores revealed a significant increase at follow-up (6 months to 3 years) compared with the preclinical results. The median IKDC score increased from 42.6 preoperatively to 75.3 at 1 year, 79.7 at 2 years, and 84.3 at 3 years. The median Cincinnati score significantly increased from 39.8 preoperatively to 72.0 at 1 year, 78.0 at 2 years, and 80.3 at 3 years. The MRI evaluation revealed a MOCART score of 82.6 at 1 year without a deterioration at the later follow-up time point. Especially, the subchondral bone analysis showed successful regeneration. All bone blocks and cancellous bone grafts were integrated in the bony defects, and no chondrocyte transplant failure could be detected throughout the follow-up. CONCLUSION: Large and deep osteochondral defects of the knee joint can be treated successfully with bone augmentation and MACT. The treatment of shallow bony defects with cancellous bone grafting and deep bony defects with bone block augmentation shows promising results.

Planimetry of mitral valve stenosis by magnetic resonance imaging.

OBJECTIVES: We sought to determine whether noninvasive planimetry of the mitral valve area (MVA) by magnetic resonance imaging (MRI) is feasible and reliable in patients with mitral stenosis (MS). BACKGROUND: Accurate assessment of MVA is particularly important for the management of patients with valvular stenosis. Current standard techniques for assessing the severity of MS include echocardiography (ECHO) and cardiac catheterization (CATH). METHODS: In 22 patients with suspected or known MS, planimetry of MVA was performed with a 1.5-T magnetic resonance scanner using a breath-hold balanced gradient echo sequence (true FISP). Data were compared with echocardiographically determined MVA (ECHO-MVA, n = 22), as well as with invasively calculated MVA by the Gorlin-formula at (CATH-MVA, n = 17). RESULTS: The correlation between MRI- and CATH-MVA was 0.89 (p < 0.0001), and the correlation between MRI- and ECHO-MVA was 0.81 (p < 0.0001). The MRI-MVA slightly overestimated CATH-MVA by 5.0% (1.60 +/- 0.45 cm(2) vs. 1.52 +/- 0.49 cm(2), p = NS) and ECHO-MVA by 8.1% (1.61 +/- 0.42 cm(2) vs. 1.48 +/- 0.42 cm(2), p < 0.05). On receiver-operating characteristic curve analysis, a value of MRI-MVA below 1.65 cm(2) indicated mitral stenosis (CATH-MVA < or =1.5 cm(2)), with a good sensitivity and specificity (89% and 75%, respectively). CONCLUSIONS: Magnetic resonance planimetry of the mitral valve orifice in mitral stenosis offers a reliable and safe method for noninvasive quantification of mitral stenosis. In the clinical management of patients with mitral stenosis, it has to be considered that planimetry by MRI slightly overestimates MVA, as compared with MVA calculated echocardiographically and at catheterization.

Dark lumen magnetic resonance enteroclysis in combination with MRI colonography for whole bowel assessment in patients with Crohn's disease: first clinical experience.

BACKGROUND: Magnetic resonance enteroclysis (MRE) is a recently introduced imaging technique that assesses the small bowel with similar sensitivity and specificity as the fluoroscopically performed conventional enteroclysis. Magnetic resonance imaging colonography (MRC) seems to be a promising technique for polyp assessment in the colon. In this feasibility study, we evaluated the combination of small bowel MRI with unprepared MRC as an integrative diagnostic approach of the whole bowel in patients with Crohn's disease. METHODS: Thirty patients with known Crohn's disease were prospectively examined. No particular colonic preparation was applied. Applying the dark lumen technique in all patients, MRE and MRC were performed within 1 session using an integrative examination protocol. T2-weighted and contrast-enhanced T1-weighted sequences were acquired. Inflammation assessment (grades 0 to 2) of the colon was compared with conventional colonoscopy in 29 patient and with surgery in 1 patient. The entire colon was graded fair to good distended in all patients. In 11 of 210 evaluated colonic segments, feces hindered an adequate intraluminal bowel assessment. Twenty-three of 30 patients had complete colonoscopy as the gold standard. In 7 patients, complete colonoscopy could not be performed because of an inflamed stenosis. RESULTS: Correct grading of colonic inflammation was performed with 55.1% sensitivity and 98.2% specificity in all segments. Considering only more extensive inflammation (grade 2), the sensitivity of MRC increased to 70.2% with a specificity of 99.2%. CONCLUSIONS: The combination of MRE and MRC could improve the diagnostic value of abdominal MRI evaluation in patients with Crohn's disease. However, MRC can not replace conventional colonoscopy in subtle inflammation assessment.

Magnetic resonance imaging gastrography: evaluation of the dark lumen technique compared with conventional gastroscopy in patients with malignant gastric disease.

OBJECTIVES: We sought to demonstrate the feasibility of depicting gastric tumors using magnetic resonance imaging (MRI) while applying the dark lumen technique. The findings were correlated with conventional gastroscopy. In addition, we evaluated the screening for lymph nodes and liver metastases during the same session to identify potential tumor spread. MATERIALS AND METHODS: The study included 15 patients with known malignant gastric disease. Conventional gastrointestinal endoscopy was performed in all patients as gold standard. All patients were examined with computed tomography for tumor staging. MRI was performed using 1 L of tap water as oral contrast agent for all protocols. The MRI program included an axial T1-weighted (T1w; 2D-FLASH) sequence, an axial STIR and T2w (TSE) sequence, and 2 postcontrast T1w (3D coronal /2D axial FLASH) sequences using 0.2 mmol/kg gadolinium diethylenetriaminepenta-acetic acid as intravenously injected contrast agent. Qualitative analysis and comparison with conventional gastroscopy were performed. RESULTS: The images obtained with the postcontrast 3D coronal T1w-FLASH sequence were the most suitable in identifying gastric tumors. Complete correlation with conventional gastroscopy was achieved in 80% of the cases and partial correlation in 13% of the cases. The same imaging sequence was also appropriate for the evaluation of lymph nodes. For the identification of liver metastases, the images obtained with the axial postcontrast T1w 2D-FLASH sequence provided a higher diagnostic confidence as compared with other imaging protocols. CONCLUSIONS: Applying the dark lumen technique through MRI is suitable for imaging gastric tumors and has the potential to become a "one-stop shopping" method because of the possibility for lymph node evaluation and screening for metastases during the same session based on the same images.

Planimetry of aortic valve area in aortic stenosis by magnetic resonance imaging.

BACKGROUND: The aim of the study was to determine whether noninvasive planimetry of aortic valve area (AVA) by magnetic resonance imaging (MRI) is feasible and reliable in patients with valvular aortic stenosis in comparison to transesophageal echocardiography (TEE) and catheterization. METHODS AND RESULTS: Planimetry of AVA by MRI (MRI-AVA) was performed on a clinical magnetic resonance system (1.5-T Sonata, Siemens Medical Solutions) in 33 patients and compared with AVA calculated invasively by the Gorlin-formula at catheterization (CATH-AVA, n = 33) as well as to AVA planimetry by multiplane TEE (TEE-AVA, n = 27). Determination of MRI-AVA was possible with an adequate image quality in 82% (27/33), whereas image quality of TEE-AVA was adequate only in 56% (15/27) of patients because of calcification artifacts (P = 0.05). The correlation between MRI-AVA and CATH-AVA was 0.80 (P < 0.0001) and the correlation of MRI-AVA and TEE-AVA was 0.86 (P < 0.0001). MRI-AVA overestimated TEE-AVA by 15% (0.98 +/- 0.31 cm2 vs. 0.85 +/- 0.3 cm2, P < 0.001) and CATH-AVA by 27% (0.94 +/- 0.29 cm2 vs. 0.74 +/- 0.24 cm2, P < 0.0001). Nevertheless, a MRI-AVA below 1,3 cm2 indicated severe aortic stenosis (CATH-AVA < 1 cm2) with a sensitivity of 96% and a specificity of 100% (ROC area 0.98). CONCLUSIONS: Planimetry of aortic valve area by MRI can be performed with better image quality as compared with TEE. In the clinical management of patients with aortic stenosis, it has to be considered that MRI slightly overestimates aortic valve area as compared with catheterization despite an excellent correlation.

Site-specific intraoperative efficacy of arthroscopic knee joint synovectomy in rheumatoid arthritis.

PURPOSE: To assess the intraoperative reduction of inflammatory infiltrates achieved by arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) with special regard to the removal site, using preoperative and postoperative synovial tissue (ST) samples. TYPE OF STUDY: A histologic and immunohistochemical study. METHODS: Eleven patients with treatment-refractory RA knee synovitis underwent arthroscopic synovectomy. In each patient, ST specimens were obtained immediately before and after synovectomy from 9 defined sites covering the whole joint. The samples were graded using an acute synovitis score (ASS; presence of polymorphonuclear neutrophilic leukocytes [PMN] and fibrin) and a chronic synovitis score (CSS; e.g., lining cell hyperplasia, presence of diffuse and lymphoid aggregates). Immunohistologic analyses were performed using 7 monoclonal antibodies directed against PMN, macrophages, and T-cell subsets (total of 1,584 preparations). Knee function was assessed after an average follow-up of 28 months by Lysholm score (modified by Klein and Jensen), Insall functional and knee scores, and Lequesne score. RESULTS: Arthroscopic synovectomy led to an overall significant (P between .005 and .05) reduction of the acute inflammatory infiltrates (ASS) by 82.1%, but to a significant reduction of chronic inflammatory infiltrates (CSS) by only 62.5%. Accordingly, the density of PMN was reduced by 81.8%, whereas that of macrophages and different T-cell subsets was only decreased by < or = 61.6%. With respect to the anatomic regions, a significantly (P < or = .05) less marked reduction of inflammatory infiltrates was observed in the upper lateral and central recess, at the medial and lateral capsule, as well as at the femoral insertion of the anterior cruciate ligament. All knee joint scores showed a significant (P < or = .01) improvement over preoperative values at follow-up. CONCLUSIONS: Arthroscopic synovectomy effectively reduces acute and chronic inflammatory infiltrates in patients with RA who have refractory synovitis of the knee joint (immediately after synovectomy) and improves knee function (28-month follow-up). However, the reduction of inflammatory infiltrates appears to depend on the anatomic region of the joint. LEVEL OF EVIDENCE: Level III.

Modern imaging using computer tomography and magnetic resonance imaging for inflammatory bowel disease (IBD) AU1.

Radiologic imaging--especially of the small bowel--plays an important role in the diagnosis and management of patients with inflammatory bowel disease. The radiographic examination of the small intestine with barium either as enteroclysis or as small bowel follow through are still the mainstays in small bowel imaging. However, abdominal CT or MRI, which has the advantage of not utilizing ionizing radiation, or the techniques of CT- or MR-enteroclysis, are overall comparable with regard to the sensitivity and specificity in detecting intestinal pathologies and have already replaced the conventional techniques in centers dedicated to the management of inflammatory bowel disease. Additionally, these cross-sectional imaging techniques provide, in a sense, a "one stop abdominal imaging workup," the diagnosis of extraluminal disease manifestations or complications. Future developments of CT- or MR-based virtual colonography and endoscopy in patients with inflammatory bowel disease are currently being investigated, but should momentarily be considered as purely experimental approaches.

3D modeling and virtual endoscopy of the small bowel based on magnetic resonance imaging in patients with inflammatory bowel disease.

RATIONALE AND OBJECTIVES: Small bowel MRI (MR imaging) is a new imaging modality that excellently depicts small intestine pathology in patients with inflammatory bowel disease. Virtual endoscopy based on sectional imaging is a recently introduced technique to create endoscopy like views. The aim of this study was to evaluate the feasibility of virtual small bowel endoscopy based on MR imaging in patients with Crohn disease. MATERIALS AND METHODS: Thirty consecutive patients with Crohn disease were scanned after oral application of pineapple juice for contrasting the small bowel. Dedicated high resolution T1 weighted 3D-FLASH sequences with fat suppression were used for volume scanning. Volume-rendered 3D models of the small bowel were created and virtual endoscopy was performed. The feasibility and quality of this new visualization method was assessed. RESULTS: In nine of 30 patients virtual endoscopy was considered as good quality (flight through the entire small bowel was possible, typical folds were revealed). In 18 patients fair quality (at least 4/5 of the small bowel were depicted adequately) was assessed. In three of 30 patients virtual endoscopy was not sufficiently possible because of inadequate bowel filling or breathing artifacts. Three fistulae diagnosed on 2D MRI were visualized on the virtual endoscopic view. CONCLUSION: Virtual endoscopy of the small bowel is feasible based on high resolution MR imaging. Vivid insight views and 3D models provide an interesting addition to sectional MR findings.

Routine skeleton radiography using a flat-panel detector: image quality and clinical acceptance at 50% dose reduction.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate image quality and clinical acceptance of a large-area, flat-panel X-ray detector for routine skeleton examinations at 50% dose reduction. METHODS: A total of 153 examinations (307 images) of 100 consecutive patients were evaluated. The cesium iodide-amorphous silicon active-matrix imager had a panel size of 43 x 43 cm, a matrix of 3000 x 3000, and a pixel pitch of 143 microm. All images were obtained with a kilovoltage setting identical to conventional radiographies of speed class 400. The amperage values were reduced by 50% compared with standard dose. Images were presented to 3 radiologists, who subjectively rated image quality on a 4-point scale according to 5 criteria (bone cortex, bone trabecula, soft tissue, overall contrast, and overall impression). Three trauma surgeons rated the clinical acceptance on a 4-point scale. Clinical acceptance was defined as directly derived consequences or therapy based on the presented image quality. For both evaluations, 1 represented excellent, 2 represented good, 3 represented moderate, and 4 represented nondiagnostic image quality/clinical acceptance. Intermediate scores at 0.5 intervals were allowed. RESULTS: The mean values for all 5 image quality criteria were rated good or excellent (< or = 2). A total of 4.2% (13 of 307) of the images were rated 2.5 to 3.5 concerning the overall impression. None of the imaging features was ranked more than 3.5 by any radiologist. The mean value of the clinical acceptance was between good and excellent (1.47). A total of 98.7% (151 of 153) of the examinations were rated < or = 2.5; 1.3% (2 of 153) of examinations were of moderate clinical acceptance (< or = 3.5). None of the examinations was of nondiagnostic image quality or clinical acceptance (>3.5); therefore, no study had to be repeated. CONCLUSION: Routine skeleton images with 50% dose reduction yield good image quality and good clinical acceptance. In cases with abundant soft tissue, less dose reduction or standard dose is required.

Magnetic resonance imaging in patients diagnosed with papilledema: a comparison of 6 different high-resolution T1- and T2(*)-weighted 3-dimensional and 2-dimensional sequences.

PURPOSE: To evaluate visualization and signal characteristics of macroscopic changes in patients with ophthalmologically stated papilledema and to find a suitable high-resolution magnetic resonance imaging (MRI) protocol. METHOD: Nine consecutive patients with 12 ophthalmologically stated papilledemas underwent MRI of the head and orbits, which consisted of the following high-resolution sequences: 3-dimensional (3D), T2*-weighted (T2*w) constructive interference in steady-state sequence (CISS); 3D, T1-weighted (T1w) magnetization prepared-rapid gradient echo sequence (MP-RAGE) (with and without intravenous contrast medium); transverse 3D and 2-dimensional (2D) (2 mm), T2-weighted (T2w) turbo spin echo (TSE); transverse 2D (2 mm), contrast-enhanced T1w TSE with fat-suppression technique; and transverse 2D (5 mm), T2w TSE. A quantitative and qualitative evaluation of the papilla, optic nerve, optic nerve sheath, optic chiasm, and the brain was performed. The 6 high-resolution sequences were compared. RESULTS: The elevation of the optic disc into the optic globe in ophthalmologically stated papilledema was best visualized in T2w, 3D CISS sequence. The pathological contrast enhancement was best seen in T1w contrast-enhanced 2D TSE sequence with fat-suppression technique. The mean width of the optic nerve sheath directly behind the globe was 7.54 mm (+/- 1.05 mm) in the pathological eyes, compared to 5.52 mm (+/- 1.11 mm) in the normal eyes. In all patients, the cerebral indices calculated showed no signs of increased intracranial pressure or other abnormalities changing the volume of the brain or ventricles. The contrast of the orbital fat versus the optic nerve sheath, the optic nerve sheath versus the surrounding cerebrospinal fluid (CSF), the surrounding CSF versus the optic nerve, the optic chiasm versus the CSF, and the optic papilla versus the optic globe were best visualized in the 3D, T2*w CISS sequence. An enhancement of the swollen optic nerve head was best seen in all 12 cases in the T1w contrast-enhanced 2D TSE sequence with fat-suppression technique. CONCLUSION: An MRI protocol consisting of a 5-mm transverse T2w TSE sequence; a T2*w, 3D CISS sequence; a T1w, 3D MP-RAGE sequence with and without contrast medium; and a transverse T1w, (2-mm) 2D TSE sequence with fat-suppression technique with intravenous contrast medium is suitable to visualize the macroscopic changes in papilledema. In addition, this combination is an excellent technique for the examination of the orbits and the brain.

Magnetic resonance imaging-based virtual endoscopy of inner ear pathology.

OBJECTIVE: To study the feasibility of high-resolution magnetic resonance imaging (MRI)-based virtual endoscopy of the labyrinth to assess subtle inner ear pathology. STUDY DESIGN: A retrospective case review of patient with known inner ear pathology to determine the feasibility and clinical value of MRI-based virtual labyrinthoscopy. SETTING: Tertiary referral center. PATIENTS: Ten patients with symptoms of sensorineural hearing loss or vertigo who underwent high-resolution MRI between 1996 and 1999. INTERVENTION: Diagnostic image modality with three-dimensional (3-D) postprocessing to assess inner ear pathology. MAIN OUTCOME MEASURES: To evaluate how 3-D rendering with virtual labyrinthoscopy can depict subtle labyrinthine pathology. RESULTS: Cases with typical 3-D models and virtual labyrinthoscopic views are presented to illustrate this new image processing approach. CONCLUSION: The virtual endoscopic view of the labyrinth revealed subtle inner ear pathology. This 3-D postprocessing technique is able to render inner surface changes of tiny structures within the inner ear. It can be performed within a very short time using dedicated hybrid rendering techniques. It allows visualization of pathology in a comprehensive way for clinicians and is able to add 3-D information for troubleshooting in doubtful two-dimensional findings. We suggest the term virtual labyrinthoscopy for virtual intraluminal visualization of the labyrinth.

Comparison of capsule endoscopy and magnetic resonance (MR) enteroclysis in suspected small bowel disease.

BACKGROUND AND AIMS: Small bowel MR enteroclysis and wireless capsule endoscopy (WCE) are new diagnostic tools for the investigation of the small bowel. The aim of this study was to compare the diagnostic yield of WCE with MR enteroclysis in the detection of small bowel pathologies. METHODS: A total of 36 patients were included in the study. Indications for imaging of the small bowel were proven or suspected small bowel Crohn's disease (CD; n=18), obscure gastrointestinal (GI) bleeding (n=14) and tumour surveillance (n=4). RESULTS: In patients with Crohn's disease WCE detected significantly more inflammatory lesions in the first two segments of the small bowel compared with MR enteroclysis (12 patients vs. 1 patient, p=0.016). In 5 out of 14 (36%) patients with GI bleeding, angiodysplasia was detected as a possible bleeding source. Three of these patients had active bleeding sites detected by WCE. One patient had scattered inflammation of the mucosa. MR enteroclysis did not reveal any intestinal abnormalities in this patient group. MR enteroclysis provided extraintestinal pathologies in 10 out of 36 (28%) patients. CONCLUSION: In patients with Crohn's disease WCE revealed significantly more inflammatory lesions in the proximal and middle part of the small bowel in comparison to MR enteroclysis, whereas in patients with obscure GI bleeding WCE was superior to MR enteroclysis.

Intraarterial gadolinium-enhanced MR angiography in humans for the detection of infrainguinal arterial stenoses before and after percutaneous angioplasty.

OBJECTIVE: The objectives of this study were to show the feasibility of intraarterial MR angiography of the infrainguinal arteries and to compare the accuracy of intraarterial MR angiography with selective intraarterial digital subtraction angiography for the detection of stenoses before and after percutaneous balloon angioplasty. SUBJECTS AND METHODS: Fifteen patients underwent digital subtraction angiography and intraarterial MR angiography before and after balloon angioplasty. For intraarterial MR angiography, 30 mL of diluted contrast agent (5 mL of gadodiamide diluted in 55 mL of 0.9% saline solution) was injected through a sheath in the superficial femoral artery using a flow rate of 2.5 mL/sec. A 3D gradient-echo sequence was performed. Four independent blinded observers assessed differences in the quantitative measurement of stenoses and localization of lesions between digital subtraction angiography and intraarterial MR angiography. The overall impression of the intraarterial MR angiography images was documented on a 4-point scale (1 = excellent, 4 = poor). Interobserver variability was calculated. RESULTS: Intraarterial MR angiography from the upper leg to the trifurcation was feasible in all 30 examinations with a mean overall impression of all segments of 1.3 (SD, 0.68). For the detection of significant stenoses (> or = 50% stenosis), the overall sensitivity and specificity for the femoropopliteal and crural vessels were 92.4% and 91.7% and 91.9% and 87.8%, respectively. For the complete leg, sensitivity and specificity were 92.2% and 88.6%, respectively. Interobserver variability for intraarterial MR angiography of the crural vessels exceeded that of the femoropopliteal arteries. CONCLUSION: Intraarterial MR angiography of the infrainguinal arteries is feasible in humans using injections of diluted contrast agent at concentrations as low as 8%. It has a high sensitivity for detecting stenoses and an acceptable interobserver variability.

New diagnostic avenues in inflammatory bowel diseases. Capsule endoscopy, magnetic resonance imaging and virtual enteroscopy.

The modalities for diagnostic imaging in patients with inflammatory bowel disease (IBD) have dramatically changed in the last decade. Several years ago the only methods to assess the small bowel were conventional enteroclysis or a small bowel 'follow through'. Nowadays, wireless capsule endoscopy as well as magnetic resonance imaging (MRI) with virtual endoscopy represent new evolving methods to depict and assess the small bowel. This article describes these recently introduced methods in the diagnostic assessment of the small bowel and discusses the clinical significance based on the current literature.

Unilateral adult malignant optic nerve glioma.

INTRODUCTION: Adult malignant optic nerve gliomas are rare and rapidly fatal visual pathway tumours. They represent a clinical entity different from the more common childhood benign optic nerve gliomas, which are frequently associated with neurofibromatosis I. CASE REPORT: A 61-year-old woman presented with rapidly progressing right vision loss, lower altitudinal visual field defect and papilloedema. MRI showed intraorbital and intracranial swelling of the right optic nerve. Resection of the intracranial part of the right optic nerve up to the chiasm revealed anaplastic astrocytoma grade III. Within 1 year, the patient died of leptomeningeal metastasis despite radiotherapy. Clinical and MRI evaluation of the left eye and optic nerve were normal at all times. DISCUSSION: Unilateral adult malignant glioma of the optic nerve is exceptional. The final diagnosis was only confirmed by optic nerve biopsy. In the literature, only one patient has been reported with a unilateral tumour manifestation; he was lost to follow-up 3 months later. All other cases were bilateral. To date, 44 case reports of adult malignant optic nerve glioma have been published, either malignant astrocytoma or glioblastoma. These tumours can mimic optic neuritis in their initial presentation. The diagnosis is seldom made before craniotomy. On MRI images, malignant glioma cannot be distinguished from optic nerve enlargement due to other causes. Although radiotherapy appears to prolong life expectancy, all presently available treatment options (radiation, surgery, radio-chemotherapy) are of limited value. Most patients go blind and die within 1 or 2 years.