Radiomics in diffusion data: a test-retest, inter- and intra-reader DWI phantom study.

AIM: The aim of this study was to evaluate the robustness of radiomics features of a MRI (magnetic resonance imaging) phantom in quantitative diffusion-weighted imaging (DWI) and depending on the image resolution. MATERIALS AND METHODS: Scanning of an in-house developed DWI phantom was performed at a 1.5 T MRI scanner (Magnetom AERA, Siemens, Erlangen, Germany) using an echo planar imaging (EPI) DWI sequence (b=0,500,1,000 s/mm2) with low (3×3 mm2) and high (2×2 mm2) image resolutions. Scans were repeated after phantom repositioning to evaluate retest reliability. Radiomics features were extracted after semi-automatic segmentation and standardised pre-processing. Intra-/interobserver reproducibility and test-retest robustness were assessed using intraclass correlation coefficients (ICC). Differences were tested with non-parametric Wilcoxon's signed-rank and Friedman's test (p < 0.05) with Dunn's post-hoc analysis. RESULTS: Test-retest ICC was overall high with >0.90 for 39/46 radiomics features in all sequences/resolutions. Decreased test-retest ICCs were pronounced for conventional Min-value (overall ICC=0.817), and grey-level zone length matrix (GLZLM) features Short-Zone Emphasis (SZE) and Short-Zone Low Grey-level Emphasis (SZLGE) (for both overall ICC=0.927). Test-retest reproducibility was significantly different between b=500, 1,000 and apparent diffusion coefficient (ADC) (mean 0.975±0.050, 0.974±0.051 and 0.966±0.063), which remained significant after post-hoc analysis between b=1,000 and ADC (p = 0.022). ICCs were not significantly different between resolutions of 2×2 and 3×3 mm2 regarding b=500 (mean: 0.977±0.052 and 0.974±0.049, p = 0.612), b=1,000 (mean: 0.973±0.059 and 0.974±0.054, p = 0.516), and ADC (mean: 0.972±0.049 and 0.955±0.101, p = 0.851). Inter- and intra-observer reliability was consistently high for all sequences (overall mean 0.992±0.021 and 0.990±0.028). CONCLUSION: Under ex-vivo conditions, DWI provided robust radiomics features with those from ADC being slightly less robust than from raw DWI (b=500, 1,000 s/mm2). No significant difference was detected for different resolutions. Although, ex-vivo reliability of DWI radiomics features was high, no implications can be made regarding in-vivo analyses.

Exploring MR regression patterns in rectal cancer during neoadjuvant radiochemotherapy with daily T2- and diffusion-weighted MRI.

BACKGROUND: To date, only limited magnetic resonance imaging (MRI) data are available concerning tumor regression during neoadjuvant radiochemotherapy (RCT) of rectal cancer patients, which is a prerequisite for adaptive radiotherapy (RT) concepts. This exploratory study prospectively evaluated daily fractional MRI during neoadjuvant treatment to analyze the predictive value of MR biomarkers for treatment response. METHODS: Locally advanced rectal cancer patients were examined with daily MRI during neoadjuvant RCT. Contouring of the tumor volume was performed for each MRI scan by using T2- and diffusion-weighted-imaging (DWI)-sequences. The daily apparent-diffusion coefficient (ADC) was calculated. Volumetric and functional tumor changes during RCT were analyzed and correlated with the pathological response after surgical resection. RESULTS: In total, 171 MRI scans of eight patients were analyzed regarding anatomical and functional dynamics during RCT. Pathological complete response (pCR) could be achieved in four patients, and four patients had a pathological partial response (pPR) following neoadjuvant treatment. T2- and DWI-based volumetry proved to be statistically significant in terms of therapeutic response, and volumetric thresholds at week two and week four during RCT were defined for the prediction of pCR. In contrast, the average tumor ADC values widely overlapped between both response groups during RCT and appeared inadequate to predict treatment response in our patient cohort. CONCLUSION: This prospective exploratory study supports the hypothesis that MRI may be able to predict pCR of rectal cancers early during neoadjuvant RCT. Our data therefore provide a useful template to tailor future MR-guided adaptive treatment concepts.

[Diffusion-weighted imaging-diagnostic supplement or alternative to contrast agents in early detection of malignancies?] / Diffusionsbildgebung ­ diagnostische Erweiterung oder Ersatz von Kontrastmitteln in der Früherkennung von Malignomen?

Medical research in the field of oncologic imaging diagnostics using magnetic resonance imaging increasingly includes diffusion-weighted imaging (DWI) sequences. The DWI sequences allow insights into different microstructural diffusion properties of water molecules in tissues depending on the sequence modification used and enable visual and quantitative analysis of the acquired imaging data. In DWI, the application of intravenous gadolinium-containing contrast agents is unnecessary and only the mobility of naturally occurring water molecules in tissues is quantified. These characteristics predispose DWI as a potential candidate for emerging as an independent diagnostic tool in selected cases and specific points in question. Current clinical diagnostic studies and the ongoing technical developments, including the increasing influence of artificial intelligence in radiology, support the growing importance of DWI. Especially with respect to selective approaches for early detection of malignancies, DWI could make an essential contribution as an eligible diagnostic tool; however, prior to discussing a broader clinical implementation, challenges regarding reliable data quality, standardization and quality assurance must be overcome.

Diffusion-weighted breast imaging.

Magnetic resonance imaging (MRI) of the breast represents one of the most sensitive imaging modalities in breast cancer detection. Diffusion-weighted imaging (DWI) is a sequence variation introduced as a complementary MRI technique that relies on mapping the diffusion process of water molecules thereby providing additional information about the underlying tissue. Since water diffusion is more restricted in most malignant tumors than in benign ones owing to the higher cellularity of the rapidly proliferating neoplasia, DWI has the potential to contribute to the identification and characterization of suspicious breast lesions. Thus, DWI might increase the diagnostic accuracy of breast MRI and its clinical value. Future applications including optimized DWI sequences, technical developments in MR devices, and the application of radiomics/artificial intelligence algorithms may expand the potential of DWI in breast imaging beyond its current supplementary role.

Maximum intensity breast diffusion MRI for BI-RADS 4 lesions detected on X-ray mammography.

AIM: To investigate an abbreviated, contrast-agent free diffusion-weighted (DW) breast magnetic resonance imaging (MRI) protocol that provides a single image for the radiologist to read in order to non-invasively examine Breast Imaging-Reporting and Data System (BI-RADS) 4 lesions detected using breast cancer screening X-ray mammography. MATERIALS AND METHODS: This retrospective evaluation within a institutional review board-approved, prospective study included 115 women (mean 57 years, range 50-69 years) with BI-RADS 4 findings on X-ray mammography and indication for biopsy over a period of 15 months. Full diagnostic breast MRI (FDP) was performed prior to biopsy (1.5 T). Maximum intensity breast diffusion (MIBD) images were generated from DW images (b = 1,500 mm/s2, 3 mm section thickness) of the breast. MIBD and T2-weighted (T2W) images were read by two radiologists and compared to the diagnostic accuracy of an expert reading of the FDP with histopathology as the reference standard. The acquisition time of MIBD and T2W MRI was about 7 minutes. RESULTS: MIBD MRI provided a diagnostic accuracy of 87.93% (95% confidence interval [CI]: 80.58-93.24%) for R1 and 89.66% (95% CI: 82.63-94.54%) for R2. Expert reading of the FDP revealed a similar accuracy of 86.2% (95% CI: 78.67-91.43%). The positive predictive value (PPV) could be increased from 36.2% (95% CI: 28.02-45.28; X-ray mammography alone) to a mean PPV of 80.89% (R1 79.17%, R2 82.16%) using MIBD MRI. Mean reading time was 30 seconds (25%/75 percentile 24.5-41.25). CONCLUSIONS: MIBD MRI might be of supplemental value if added to the work-up of BI-RADS 4 X-ray mammography screening findings. MIBD MRI might help reduce the false-positive rate prior to biopsy for reference lesions at only limited expense of measurement and reading time.

[Selected clinically established and scientific techniques of diffusion-weighted MRI. In the context of imaging in oncology]. / Ausgewählte klinisch etablierte und wissenschaftliche Techniken der diffusionsgewichteten MRT. Im Kontext der onkologischen Bildgebung.

BACKGROUND: Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that was established in the clinical routine primarily for the detection of brain ischemia. In the past 15 years its clinical use has been extended to oncological radiology, as tumor and metastases can be depicted in DWI due to their hypercellular nature. PRINCIPLES: The basis of DWI is the Stejskal-Tanner experiment. The diffusion properties of tissue can be visualized after acquisition of at least two diffusion-weighted series using echo planar imaging and a specific sequence of gradient pulses. CLINICAL APPLICATIONS: The use of DWI in prostate MRI was reported to be one of the first established applications that found its way into internationally recognized clinical guidelines of the European Society of Urological Radiology (ESUR) and the prostate imaging reporting and data system (PI-RADS) scale. Due to recently reported high specificity and negative predictive values of 94% and 92%, respectively, its regular use for breast MRI is expected in the near future. Furthermore, DWI can also reliably be used for whole-body imaging in patients with multiple myeloma or for measuring the extent of bone metastases. OUTLOOK: New techniques in DWI, such as intravoxel incoherent motion imaging, diffusion kurtosis imaging and histogram-based analyses represent promising approaches to achieve a more quantitative evaluation for tumor detection and therapy response.

Quantitative in vivo analysis of small bowel motility using MRI examinations in mice--proof of concept study.

Small bowel motility analyses using magnetic resonance imaging (MRI) could reduce current invasive techniques in animal studies and comply with the 'three Rs' rule for human animal experimentation. Thus we investigated the feasibility of in vivo small bowel motility analyses in mice using dynamic MRI acquisitions. All experimental procedures were approved by the institutional animal care committee. Six C57BL/6 mice underwent MRI without additional preparation after isoflurane anaesthetization in the prone position on a 4.7 T small animal imager equipped with a linear polarized hydrogen birdcage whole-body mouse coil. Motility was assessed using a true fast imaging in a steady precession sequence in the coronal orientation (acquisition time per slice 512 ms, in-plane resolution 234 × 234 µm, matrix size 128 × 128, slice thickness 1 mm) over 30 s corresponding to 60 acquisitions. Motility was manually assessed measuring the small bowel diameter change over time. The resulting motility curves were analysed for the following parameters: contraction frequency per minute (cpm), maximal contraction amplitude (maximum to minimum [mm]), luminal diameter (mm) and luminal occlusion rate. Small bowel motility quantification was found to be possible in all animals with a mean small bowel contraction frequency of 10.67 cpm (SD ± 3.84), a mean amplitude of the contractions of 1.33 mm (SD ± 0.43) and a mean luminal diameter of 1.37 mm (SD ± 0.42). The mean luminal occlusion rate was 1.044 (SD ± 0.45%/100). The mean duration needed for a single motility assessment was 185 s (SD ± 54.02). Thus our study demonstrated the feasibility of an easy and time-sparing functional assessment for in vivo small bowel motility analyses in mice. This could improve the development of small animal models of intestinal diseases and provide a method similar to clinical MR examinations that is in concordance with the 'three Rs' for humane animal experimentation.

Software-assisted quantitative analysis of small bowel motility compared to manual measurements.

AIM: To validate a newly developed software prototype that automatically analyses small bowel motility by comparing it directly with manual measurement. MATERIAL AND METHODS: Forty-five patients with clinical indication for small bowel magnetic resonance imaging (MRI) were retrospectively included in this institutional review board-approved study. MRI was performed using a 1.5 T system following a standard MR-enterography protocol. Small bowel motility parameters (contractions-per-minute, luminal diameter, amplitude) were measured three times each in identical segments using the manual and the semiautomatic software-assisted method. The methods were compared for agreement, repeatability, and time needed for each measurement. All parameters were compared between the methods. RESULTS: A total of 91 small-bowel segments were analysed. No significant intra-individual difference (p > 0.05) was found for peristaltic frequencies between the methods (mean: 4.14/min manual; 4.22/min software-assisted). Amplitudes (5.14 mm; 5.57 mm) and mean lumen diameters (17.39 mm; 14.68) differed due to systematic differences in the definition of the bowel wall. Mean duration of single measurement was significantly (p < 0.01) shorter with the software (6.25 min; 1.30 min). The scattering of repeated measurements was significantly (p < 0.05) lower using the software. CONCLUSION: The software-assisted method accomplished highly reliable, fast and accurate measurement of small bowel motility. Measurement precision and duration differed significantly between the two methods in favour of the software-assisted technique.

Gadoxetate uptake as a possible marker of hepatocyte damage after liver resection-preliminary data.

AIM: To determine the feasibility of evaluating surgically induced hepatocyte damage using gadoxetate disodium (Gd-EOB-DTPA) as a marker for viable hepatocytes at magnetic resonance imaging (MRI) after liver resection. MATERIAL AND METHODS: Fifteen patients were prospectively enrolled in this institutional review board-approved study prior to elective liver resection after informed consent. Three Tesla MRI was performed 3-7 days after surgery. Three-dimensional (3D) T1-weighted (W) volumetric interpolated breath-hold gradient echo (VIBE) sequences covering the liver were acquired before and 20 min after Gd-EOB-DTPA administration. The signal-to-noise ratio (SNR) was used to compare the uptake of Gd-EOB-DTPA in healthy liver tissue and in liver tissue adjacent to the resection border applying paired Student's t-test. Correlations with potential influencing factors (blood loss, duration of intervention, age, pre-existing liver diseases, postoperative change of resection surface) were calculated using Pearson's correlation coefficient. RESULTS: Before Gd-EOB-DTPA administration the SNR did not differ significantly (p = 0.052) between healthy liver tissue adjacent to untouched liver borders [59.55 ± 25.46 (SD)] and the liver tissue compartment close to the resection surface (63.31 ± 27.24). During the hepatocyte-specific phase, the surgical site showed a significantly (p = 0.04) lower SNR (69.44 ± 24.23) compared to the healthy site (78.45 ± 27.71). Dynamic analyses revealed a significantly lower increase (p = 0.008) in signal intensity in the healthy tissue compared to the resection border compartment. CONCLUSION: EOB-DTPA-enhanced MRI may have the potential to be an effective non-invasive tool for detecting hepatocyte damage after liver resection.

Differentiation between active and chronic Crohn's disease using MRI small-bowel motility examinations - initial experience.

AIM: To evaluate the influence of locally active Crohn's disease on systemic small-bowel motility in patients with chronic Crohn's disease compared to healthy individuals. MATERIAL AND METHODS: Fifteen healthy individuals (11 men, four women; mean age 37 years) and 20 patients with histopathologically proven active (n = 15; 10 women, 5 men; mean age 45 years) or chronic (n = 5; four women, one man; mean age 48 years) Crohn's disease were included in this institutional review board-approved, retrospective study. Magnetic resonance imaging (MRI; 1.5 T) was performed after standardized preparation. Two-dimensional (2D) cine sequences for motility acquisition were performed in apnoea (27 s). Motility assessment was performed using dedicated software in three randomly chosen areas of the small-bowel outside known Crohn's disease-affected hotspots. The main quantitative characteristics (frequency, amplitude, occlusion rate) were compared using Student's t-test and one-way analysis of variance (ANOVA). RESULTS: Three randomly chosen segments were analysed in each participant. Patients with active Crohn's disease had significantly (p < 0.05) reduced contraction frequencies (active Crohn's disease: 2.86/min; chronic: 4.14/min; healthy: 4.53/min) and luminal occlusion rates (active: 0.43; chronic: 0.70; healthy: 0.73) compared to healthy individuals and patients with chronic Crohn's disease. Contraction amplitudes were significantly reduced during active Crohn's disease (6.71 mm) compared to healthy participants (10.14 mm), but this only reached borderline significance in comparison to chronic Crohn's disease (8.87 mm). Mean bowel lumen diameter was significantly (p = 0.04) higher in patients with active Crohn's disease (16.91 mm) compared to healthy participants (14.79 mm) but not in comparison to patients with chronic Crohn's disease (13.68). CONCLUSION: The findings of the present study suggest that local inflammatory activity of small-bowel segments in patients with active Crohn's disease alters small-bowel motility in distant, non-affected segments. The motility patterns revealed reduced contraction-wave frequencies, amplitudes, and decreased luminal occlusion rates. Thus evaluation of these characteristics potentially helps to differentiate between chronic and active Crohn's disease.

MR imaging in Crohn's disease: correlation of MR motility measurement with histopathology in the terminal ileum.

BACKGROUND: The objective of the study was to correlate MR-detectable motility alterations of the terminal ileum with biopsy-documented active and chronic changes in Crohn's disease. METHODS: This IRB approved retrospective analysis of 43 patients included magnetic resonance enterography (MRE) and terminal ileum biopsies (<2 weeks apart). Motility was measured at the terminal ileum using coronal 2D trueFISP pulse sequences (1.5T MRI,TR 83.8,TE1.89) and dedicated motility assessment software. Motility grading (hypermotility, normal, hypomotility, complete arrest) was agreed by two experienced readers. Motility was compared and correlated with histopathology using two-tailed Kruskal-Wallis test and paired Spearman Rank-Order Correlation tests. KEY RESULTS: Motility abnormalities were present in 27/43 patients: nine hypomotility and 18 complete arrest. Active disease was diagnosed on 15 biopsies: eight moderate and seven severe inflammatory activity. Chronic changes were diagnosed on 17 biopsies: 13 moderate and four severe cases. In four patients with normal motility alterations on histopathology were diagnosed. Histopathology correlated with presence (P = 0.0056 for hypomotility and P = 0.0119 for complete arrest) and grade (P < 0.0001; P = 0.0004) of motility alterations. A significant difference in the motility was observed in patients with active or chronic CD compared with patients without disease (P < 0.001; P = 0.0024). CONCLUSIONS & INFERENCES: MR-detectable motility changes of the terminal ileum correlate with histopathological findings both in active and chronic CD. Motility changes may indicate the presence pathology, but do not allow differentiation of active and chronic disease.

Crohn's disease: small bowel motility impairment correlates with inflammatory-related markers C-reactive protein and calprotectin.

BACKGROUND: To evaluate the correlation between the levels of C-reactive protein (CRP), calprotectin, and small bowel motility in patients with Crohn's disease assessed with MRI. METHODS: This prospective institutional review board approved study included magnetic resonance imaging enterography (MRE) and analyses of inflammatory markers in blood (C-reactive protein) and feces (calprotectin). For cine MRE, a coronal 2D-T2w sequence was used on a 1.5 T MRI system. Small bowel motility was analyzed in 13 patients using dedicated magnetic resonance MR-motility assessment software (Motasso). Contraction frequency, amplitude, amplitude diameter ratio, and luminal diameter were determined as well as the blood levels of CRP (mg L(-1) ) and fecal levels of calprotectin (ug g(-1) ). Statistics were calculated using Pearson's correlation coefficient. KEY RESULTS: A significant inverse linear correlation was found between the contraction frequency and both the level of CRP (r = -0.701, P = 0.008) and calprotectin (r = -0.805, P = 0.001). Dilatation of small bowel diameter significantly correlated with calprotectin levels (r = 0.857, P =< 0.001) but not with CRP (r = 0.447, P = 0.126). The absolute amplitude of the contractions did not correlate neither with the level of CRP (r = -0.527, P = 0.064) nor with calprotectin (r = -0.612, P = 0.026). The ratio describing the contraction amplitude relatively to the individual luminal diameter significantly correlated with calprotectin (r = 0.736, P = 0.004) and with CRP (r = 0.577, P = 0.039). CONCLUSIONS & INFERENCES: Alterations of small bowel motility during CD flares significantly correlate with the level of calprotectin and CRP indicating that they represent inflammatory activity.