Reproducibility Of Apparent Diffusion Coefficient Research Articles

Prostate diffusion-weighted imaging (DWI) in MR-guided radiotherapy: Reproducibility assessment on 1.5 T MR-Linac and 1.5 T MR-simulator

PurposeDiffusion-weighted imaging (DWI) holds promise for image-guided radiotherapy (MRgRT) in prostate cancer. However, challenges persist due to image distortion, artifacts, and apparent diffusion coefficient (ADC) reproducibility issues. This study aimed to assess DWI image quality and ADC reproducibility on both a 1.5 T MR-simulator and a 1.5 T MR-Linac, employing measurements from both an ACR MRI phantom and prostate cancer patients undergoing MRgRT. MethodsDW-MRI scans were conducted on 19 patients (mean age = 69 ± 8 years, with 23 MR-visible intra-prostatic lesions) and an ACR MRI phantom using a 1.5 T MR-simulator (b-values = 0, 800, 1400s/mm2) and a 1.5 T MR-Linac (b-values = 50, 500, 800 s/mm2). ADC homogeneity in the phantom was evaluated via 1D profile flatness (FL) in three directions. Image quality was assessed through qualitative 5-point Likert scale ratings and quantitative ADC and signal-to-noise ratio (SNR) measurements. Intra-observer reproducibility of image quality scores was evaluated using ICC(1, 2). Geometric distortion was measured by comparing landmark sizes on the ACR phantom against the ground truth. Mean ADC and reproducibility were assessed using Bland-Altman plots. ResultsBoth MR-simulator and MR-Linac demonstrated high ADC homogeneity (FL > 87.5% - MR-simulator: 97.23 ± 0.62%, MR-Linac: 94.75 ± 0.62%, p < 0.05) in the phantom. Image quality scores revealed acceptable ratings (≥3) for capsule demarcation, image artifacts, and geometric distortion in patients. However, intra-prostatic lesions were barely discernible in b800 images for both MR-simulator (average score = 2.37 ± 1.33) and MR-Linac (average score = 2.16 ± 1.28). While MR-Linac DWI scans exhibited significantly more severe geometric distortion than MR-simulator scans (p < 0.01), most phantom measurements fell within the image in-plane resolution of 3 mm. Significant differences were noted in MR-simulator ADC (CTV: 1.20 ± 0.14 × 10−3 mm2/s (MR-simulator) vs 1.06 ± 0.10 × 10–3 mm2/s (MR-Linac); GTV: 1.05 ± 0.21 × 10−3 mm2/s vs 0.91 ± 0.16 × 10 mm2/s, all p < 0.05), with a small non-zero bias observed in the Bland-Altman analysis (CTV: 12.3%; GTV: 14.5%). ConclusionThe significantly larger MR-simulator ADC and the small non-zero bias hint at potential systematic differences in ADC values acquired from an MR-simulator and an MR-Linac, both at 1.5 T. Although acceptable ADC homogeneity was noted, caution is warranted in interpreting MR-Linac DWI images due to occasional severe artifacts. Further studies are essential to validate DWI and ADC as reliable imaging markers in prostate cancer MRgRT.

Reproducibility of diffusion-weighted magnetic resonance imaging in head and neck cancer assessed on a 1.5 T MR-Linac and comparison to parallel measurements on a 3 T diagnostic scanner

Background and purposeBefore quantitative imaging biomarkers (QIBs) acquired with magnetic resonance imaging (MRI) can be used for interventional trials in radiotherapy (RT), technical validation of these QIBs is necessary. The aim of this study was to assess the reproducibility of apparent diffusion coefficient (ADC) values, derived from diffusion-weighted (DW) MRI, in head and neck cancer using a 1.5 T MR-Linac (MRL) by comparison to a 3 T diagnostic scanner (DS). Material and methodsDW-MRIs were acquired on MRL and DS for 15 head and neck cancer patients before RT and in week 2 and rigidly registered to the planning computed tomography. Mean ADC values were calculated for submandibular (SG) and parotid (PG) glands as well as target volumes (TV, gross tumor volume and lymph nodes), which were delineated based on computed tomography. Mean absolute ADC differences as well as within-subject coefficient of variation (wCV) and intraclass correlation coefficients (ICCs) were calculated for all volumes of interest. ResultsA total of 23 datasets were analyzed. Mean ADC difference (DS-MRL) for SG, PG and TV resulted in 142, 254 and 93·10-6 mm2/s. wCVs/ICCs, comparing MRL and DS, were determined as 13.7 %/0.26, 24.4 %/0.23 and 16.1 %/0.73 for SG, PG and TV, respectively. ConclusionADC values, measured on the 1.5 T MRL, showed reasonable reproducibility with an ADC underestimation in contrast to the DS. This ADC shift must be validated in further experiments and considered for future translation of QIB candidates from DS to MRL for response adaptive RT.

Multisite MRI Intravoxel Incoherent Motion Repeatability and Reproducibility across 3 T Scanners in a Breast Diffusion Phantom: A BReast Intravoxel Incoherent Motion Multisite (BRIMM) Study.

Monoexponential apparent diffusion coefficient (ADC) and biexponential intravoxel incoherent motion (IVIM) analysis of diffusion-weighted imaging is helpful in the characterization of breast tumors. However, repeatability/reproducibility studies across scanners and across sites are scarce. To evaluate the repeatability and reproducibility of ADC and IVIM parameters (tissue diffusivity (Dt), perfusion fraction (Fp) and pseudo-diffusion (Dp)) within and across sites employing MRI scanners from different vendors utilizing 16-channel breast array coils in a breast diffusion phantom. Phantom repeatability. A breast phantom containing tubes of different polyvinylpyrrolidone (PVP) concentrations, water, fat, and sponge flow chambers, together with an MR-compatible liquid crystal (LC) thermometer. Bipolar gradient twice-refocused spin echo sequence and monopolar gradient single spin echo sequence at 3 T. Studies were performed twice in each of two scanners, located at different sites, on each of 2 days, resulting in four studies per scanner. ADCs of the PVP and water were normalized to the vendor-provided calibrated values at the temperature indicated by the LC thermometer for repeatability/reproducibility comparisons. ADC and IVIM repeatability and reproducibility within and across sites were estimated via the within-system coefficient of variation (wCV). Pearson correlation coefficient (r) was also computed between IVIM metrics and flow speed. A P value <0.05 was considered statistically significant. ADC and Dt demonstrated excellent repeatability (<2%; <3%, respectively) and reproducibility (both <5%) at the two sites. Fp and Dp exhibited good repeatability (mean of two sites 3.67% and 5.59%, respectively) and moderate reproducibility (mean of two sites 15.96% and 13.3%, respectively). The mean intersite reproducibility (%) of Fp/Dp/Dt was 50.96/13.68/5.59, respectively. Fp and Dt demonstrated high correlations with flow speed while Dp showed lower correlations. Fp correlations with flow speed were significant at both sites. IVIM reproducibility results were promising and similar to ADC, particularly for Dt. The results were reproducible within both sites, and a progressive trend toward reproducibility across sites except for Fp. 2 TECHNICAL EFFICACY: Stage 1.

Development and benchmarking diffusion magnetic resonance imaging analysis for integration into radiation treatment planning.

The rising promise in the utility of advanced multi-parametric magnetic resonance (MR) imaging in radiotherapy (RT) treatment planning creates a necessity for testing and enhancing the accuracy of quantitative imaging analysis. Standardizing the analysis of diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) to generate meaningful and reproducible apparent diffusion coefficient (ADC) and fractional anisotropy (FA) lays the requisite needed for clinical integration. The aim of the demonstrated work is to benchmark the generation of the ADC and FA parametric map analyses using integrated tools in a commercial treatment planning system against the currently used ones. Three software packages were used for generating ADC and FA maps in this study; one tool was developed within a commercial treatment planning system, another by the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library FSL (Analysis Group, FMRIB, Oxford, United Kingdom), and an in-house tool developed at the M.D. Anderson Cancer Center. The ADC and FA maps generated by all three packages for 35 subjects were subtracted from one another, and the standard deviation of the images' differences was used to compare the reproducibility. The reproducibility of the ADC maps was compared with the Quantitative Imaging Biomarkers Alliance (QIBA) protocol, while that of the FA maps was compared to data in published literature. Results show that the discrepancies between the ADC maps calculated for each patient using the three different software algorithms are less than 2% which meets the 3.6% recommended QIBA requirement. Except for a small number of isolated points, the majority of differences in FA maps for each patient produced by the three methods did not exceed 0.02 which is 10 times lower than the differences seen in healthy gray and white matter. The results were also compared to the maps generated by existing MR Imaging consoles and showed that the robustness of console generated ADC and FA maps is largely dependent on the correct application of scaling factors, that only if correctly placed; the differences between the three tested methods and the console generated values were within the recommended QIBA guidelines. Cross-comparison difference maps demonstrated that quantitative reproducibility of ADC and FA metrics generated using our tested commercial treatment planning system were comparable to in-house and established tools as benchmarks. This integrated approach facilitates the clinical utility of diffusion imaging in radiation treatment planning workflow.

Recommendations for improved reproducibility of ADC derivation on behalf of the Elekta MRI-linac consortium image analysis working group

Background and purposeThe apparent diffusion coefficient (ADC), a potential imaging biomarker for radiotherapy response, needs to be reproducible before translation into clinical use. The aim of this study was to evaluate the multi-centre delineation- and calculation-related ADC variation and give recommendations to minimize it. Materials and methodsNine centres received identical diffusion-weighted and anatomical magnetic resonance images of different cancerous tumours (adrenal gland, pelvic oligo metastasis, pancreas, and prostate). All centres delineated the gross tumour volume (GTV), clinical target volume (CTV), and viable tumour volume (VTV), and calculated ADCs using both their local calculation methods and each of the following calculation conditions: b-values 0–500 vs. 150–500 s/mm2, region-of-interest (ROI)-based vs. voxel-based calculation, and mean vs. median. ADC variation was assessed using the mean coefficient of variation across delineations (CVD) and calculation methods (CVC). Absolute ADC differences between calculation conditions were evaluated using Friedman’s test. Recommendations for ADC calculation were formulated based on observations and discussions within the Elekta MRI-linac consortium image analysis working group. ResultsThe median (range) CVD and CVC were 0.06 (0.02–0.32) and 0.17 (0.08–0.26), respectively. The ADC estimates differed 18% between b-value sets and 4% between ROI/voxel-based calculation (p-values < 0.01). No significant difference was observed between mean and median (p = 0.64). Aligning calculation conditions between centres reduced CVC to 0.04 (0.01–0.16). CVD was comparable between ROI types. ConclusionOverall, calculation methods had a larger impact on ADC reproducibility compared to delineation. Based on the results, significant sources of variation were identified, which should be considered when initiating new studies, in particular multi-centre investigations.

Abdominal Diffusion-Weighted MRI With Simultaneous Multi-Slice Acquisition: Agreement and Reproducibility of Apparent Diffusion Coefficients Measurements.

Simultaneous multi-slice diffusion-weighted imaging (SMS-DWI) can shorten acquisition time in abdominal imaging. To investigate the agreement and reproducibility of apparent diffusion coefficient (ADC) from abdominal SMS-DWI acquired with different vendors and different breathing schemes. Prospective. Twenty volunteers and 10 patients. 3.0 T, SMS-DWI with a diffusion-weighted echo-planar imaging sequence. SMS-DWI was acquired using breath-hold and free-breathing techniques in scanners from two vendors, yielding four scans in each participant. Average ADC values were measured in the liver, pancreas, spleen, and both kidneys. Non-normalized ADC and ADCs normalized to the spleen were compared between vendors and breathing schemes. Paired t-test or Wilcoxon signed rank test; intraclass correlation coefficient (ICC); Bland-Altman method; coefficient of variation (CV) analysis; significance level: P < 0.05. Non-normalized ADCs from the four SMS-DWI scans did not differ significantly in the spleen (P = 0.262, 0.330, 0.166, 0.122), right kidney (P = 0.167, 0.538, 0.957, 0.086), and left kidney (P = 0.182, 0.281, 0.504, 0.405), but there were significant differences in the liver and pancreas. For normalized ADCs, there were no significant differences in the liver (P = 0.315, 0.915, 0.198, 0.799), spleen (P = 0.815, 0.689, 0.347, 0.423), pancreas (P = 0.165, 0.336, 0.304, 0.584), right kidney (P = 0.165, 0.336, 0.304, 0.584), and left kidney (P = 0.496, 0.304, 0.443, 0.371). Inter-reader agreements of non-normalized ADCs were good to excellent (ICCs ranged from 0.861 to 0.983), and agreement and reproducibility were good to excellent depending on anatomic location (CVs ranged from 3.55% to 13.98%). Overall CVs for abdominal ADCs from the four scans were 6.25%, 7.62%, 7.08, and 7.60%. The normalized ADCs from abdominal SMS-DWI may be comparable between different vendors and breathing schemes, showing good agreement and reproducibility. ADC changes above approximately 8% may potentially be considered as a reliable quantitative biomarker to assess disease or treatment-related changes. 2 TECHNICAL EFFICACY: Stage 2.

RESOLVE-based radiomics in cervical cancer: improved image quality means better feature reproducibility?

To compare the reproducibility of apparent diffusion coefficient (ADC)-based radiomic features between readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) and single-shot echo-planar diffusion-weighted imaging (SS-EPI DWI) in cervical cancer. The RESOLVE and SS-EPI DWI images of 36 patients with histopathologically confirmed cervical cancer were collected retrospectively. Two observers independently delineated the whole tumour on RESOLVE and SS-EPI DWI, and then copied them to the corresponding ADC maps. Shape, first-order, and texture features were extracted from ADC maps in the original and filtered (Laplacian of Gaussian [LoG] and wavelet) images. Thereafter, 1,316 features were generated in each RESOLVE and SS-EPI DWI, respectively. The reproducibility of radiomic features was assessed using intraclass correlation coefficient (ICC). In the original images, RESOLVE showed 92.86%, 66.67%, and 86.67% of features with excellent reproducibility in shape, first-order, and texture features, while SS-EPI DWI showed 85.71%, 72.22%, and 60% of features with excellent reproducibility, respectively. In the LoG and wavelet filtered images, RESOLVE had 56.77% and 65.32% of features with excellent reproducibility and SS-EPI DWI had 44.95% and 61.96% of features with excellent reproducibility, respectively. Compared with SS-EPI DWI, the feature reproducibility of RESOLVE was better in cervical cancer, especially for texture features. The filtered images cannot improve the feature reproducibility compared with the original images for both SS-EPI DWI and RESOLVE.

Motion-robust, blood-suppressed, reduced-distortion diffusion MRI of the liver.

To evaluate feasibility and reproducibility of liver diffusion-weighted (DW) MRI using cardiac-motion-robust, blood-suppressed, reduced-distortion techniques. DW-MRI data were acquired at 3T in an anatomically accurate liver phantom including controlled pulsatile motion, in eight healthy volunteers and four patients with known or suspected liver metastases. Standard monopolar and motion-robust (M1-nulled, and M1-optimized) DW gradient waveforms were each acquired with single-shot echo-planar imaging (ssEPI) and multishot EPI (msEPI). In the motion phantom, apparent diffusion coefficient (ADC) was measured in the motion-affected volume. In healthy volunteers, ADC was measured in the left and right liver lobes separately to evaluate ADC reproducibility between the two lobes. Image distortions were quantified using the normalized cross-correlation coefficient, with an undistorted T2-weighted reference. In the motion phantom, ADC mean and SD in motion-affected volumes substantially increased with increasing motion for monopolar waveforms. ADC remained stable in the presence of increasing motion when using motion-robust waveforms. M1-optimized waveforms suppressed slow flow signal present with M1-nulled waveforms. In healthy volunteers, monopolar waveforms generated significantly different ADC measurements between left and right liver lobes ( , reproducibility coefficients (RPC)= mm /s for monopolar-msEPI), while M1-optimized waveforms showed more reproducible ADC values ( , mm /s for M1-optimized-msEPI). In phantom and healthy volunteer studies, motion-robust acquisitions with msEPI showed significantly reduced image distortion ( ) compared to ssEPI. Patient scans showed reduction of wormhole artifacts when combining M1-optimized waveforms with msEPI. Synergistic effects of combined M1-optimized diffusion waveforms and msEPI acquisitions enable reproducible liver DWI with motion robustness, blood signal suppression, and reduced distortion.

Comparing the clinical utility of single-shot, readout-segmented and zoomit echo-planar imaging in diffusion-weighted imaging of the kidney at 3 T

We compared the clinical utility of single-shot echo-planar imaging (SS-EPI) using different breathing schemes, readout-segmented EPI and zoomit EPI in the repeatability of apparent diffusion coefficient (ADC) measurements, cortico-medullary contrast to noise ratio (c-mCNR) and image quality. In this institutional review board-approved prospective study, some common clinically applicable diffusion-weighted imaging (b = 50, 400, 800 s/mm2) of kidney on 3.0 T MRI were performed on 22 volunteers using SS-EPI with breath-hold diffusion-weighted imaging (BH-DWI), free-breathing (FB-DWI), navigator-triggered (NT-DWI) and respiratory-triggered (RT-DWI), readout-segmented DWI (RS-DWI), and Zoomit DWI (Z-DWI). ADC and c-mCNR were measured in 12 anatomic locations (the upper, middle, and lower pole of the renal cortex and medulla), and image quality was assessed on these DWI sequences. A DWI with the optimal clinical utility was decided by systematically assessing the ADC repeatability, c-mCNR and image quality among the DWIs. For ADC measurements, Z-DWI had an excellent intra-observer agreement (intra-class correlation coefficients (ICCs): 0.876–0.944) and good inter-observer agreement (inter-class ICCs: 0.798–0.856) in six DWI sequences. Z-DWI had the highest ADC repeatability in most of the 12 anatomic locations of the kidneys (mean ADC absolute difference: 0.070–0.111 × 10−3 mm2/s, limit of agreement: 0.031–0.056 × 10−3 mm2/s). In all DWIs, Z-DWI yielded a slightly higher c-mCNR than other DWIs in most representative locations (P > 0.05), which was significantly higher than BH-DWI and FB-DWI in the middle pole of both kidneys and the upper pole of the left kidney (P < 0.05). In addition, Z-DWI yielded image quality that was similar to RT-DWI and NT-DWI (P > 0.05) and superior to BH-DWI, FB-DWI and RS-DWI (P < 0.05). Our results suggest that Z-DWI provides the highest ADC reproducibility, better c-mCNR and good image quality on 3.0 T MRI, making it the recommended sequence for clinical DWI of the kidney.

Long-Term Stability of Gradient Characteristics Warrants Model-Based Correction of Diffusion Weighting Bias.

The study aims to test the long-term stability of gradient characteristics for model-based correction of diffusion weighting (DW) bias in an apparent diffusion coefficient (ADC) for multisite imaging trials. Single spin echo (SSE) DWI of a long-tube ice-water phantom was acquired quarterly on six MR scanners over two years for individual diffusion gradient channels, along with mapping, as a function of right-left (RL) and superior-inferior (SI) offsets from the isocenter. Additional double spin-echo (DSE) DWI was performed on two systems. The offset dependences of derived ADC were fit to 4th-order polynomials. Chronic shim gradients were measured from spatial derivatives of maps along the tube direction. Gradient nonlinearity (GNL) was modeled using vendor-provided gradient field descriptions. Deviations were quantified by root-mean-square differences (RMSD), normalized to reference ice-water ADC, between the model and reference (), measurement and model (), and temporal measurement variations (). Average was 4.9 ± 3.2 (%RL) and –14.8 ± 3.8 (%SI), and threefold larger than . was close to measurement errors (~3%). GNL-induced bias across gradient systems varied up to 20%, while deviation from the model accounted at most for 6.5%, and temporal variation for less than 3% of ADC reproducibility error. Higher SSE = 7.5–11% was reduced to 2.5–4.8% by DSE, consistent with the eddy current origin. Measured chronic shim gradients below 0.1 mT/m had a minor contribution to ADC bias. The demonstrated long-term stability of spatial ADC profiles and consistency with system GNL models justifies retrospective and prospective DW bias correction based on system gradient design models. Residual errors due to eddy currents and shim gradients should be corrected independent of GNL.

Diffusion kurtosis imaging for assessing endometrial fibrosis: a preliminary clinical study.

To investigate the feasibility of using diffusion kurtosis imaging (DKI) for the assessment of endometrial fibrosis. 40 patients with hysteroscopy confirmed endometrial fibrosis and 30 healthy women underwent MR examination including the DKI sequence (b = 0, 500, 1000, 1500, and 2000 s/mm2). Endometrial thickness (ET), apparent diffusion coefficient (ADC), corrected ADC (D), and kurtosis of diffusion (K) were measured and compared, and the diagnostic performance of those parameters was evaluated using ROC curves analysis. Patients with endometrial fibrosis had a thinner endometrium than the healthy controls (P < 0.001). They also had significantly lower ADC and D values and significantly higher K values of the endometrium than the healthy controls (all P < 0.001). ADC, D, K, and ET all performed excellently in diagnosing endometrial fibrosis, with areas under the curve (AUCs) of 0.940, 0.879, 0.860, and 0.853, respectively. ADC showed the highest AUC, demonstrating better diagnostic accuracy than K (z = 2.307, P < 0.05). However, there were no differences in AUC between D, K, and ET, or ADC, D, and ET (all P > 0.05). The reproducibility of ADC, D, and K values in patients with endometrial fibrosis and healthy controls was excellent (ICC 0.951-0.991). DKI of the endometrium has promising potential for the noninvasive assessment of endometrial fibrosis.

Repeatability and Reproducibility of ADC Measurements and MRI Signal Intensity Measurements of Bone Marrow in Monoclonal Plasma Cell Disorders: A Prospective Bi-institutional Multiscanner, Multiprotocol Study.

Apparent diffusion coefficient (ADC) and signal intensity (SI) measurements play an increasing role in magnetic resonance imaging (MRI) of monoclonal plasma cell disorders. The purpose of this study was to assess interrater variability, repeatability, and reproducibility of ADC and SI measurements from bone marrow (BM) under variation of MRI protocols and scanners. Fifty-five patients with suspected or confirmed monoclonal plasma cell disorder were prospectively included in this institutional review board-approved study and underwent several measurements after the standard clinical whole-body MR scan, including repeated scan after repositioning, scan with a second MRI protocol, scan at a second 1.5 T scanner with a harmonized MRI protocol, and scan at a 3 T scanner. For T1-weighted, T2-weighted STIR, B800 images, and ADC maps, regions of interest were placed in the BM of the iliac crest and sacral bone, and in muscle tissue for image normalization. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. Interrater variability and repeatability experiments showed a maximal relative bias of -0.077 and a maximal coefficient of variation of 16.2% for all sequences. Although the deviations at the second 1.5 T scanner with harmonized MRI protocol to the first 1.5 T scanner showed a maximal relative bias of 0.124 for all sequences, the variation of the MRI protocol and scan at the 3 T scanner led to large relative biases of up to -0.357 and -0.526, respectively. When comparing the 3 T scanner to the 1.5 T scanner, normalization to muscle reduced the bias of T1-weighted and T2-weighted sequences, but not of ADC maps. The MRI scanners with identical field strength and harmonized MRI protocols can provide relatively stable quantitative measurements of BM ADC and SI. Deviations in MRI field strength and MRI protocol should be avoided when applying ADC cutoff values, which were established at other scanners or when performing multicentric imaging trials.

Noninvasive assessment of endometrial fibrosis in patients with intravoxel incoherent motion MR imaging

Recently, few noninvasive methods have been reported to evaluate endometrial fibrosis. Our study was to investigate the feasibility of intravoxel incoherent motion (IVIM) MR imaging in the detection of endometrial fibrosis in patients with intrauterine injury. 30 patients with hysteroscopy-confirmed endometrial fibrosis and 28 healthy women were enrolled to undergo MR examination including the IVIM sequence. Endometrial thickness (ET); apparent diffusion coefficient (ADC); and IVIM parameters, including pure diffusion coefficient (D), pseudodiffusion coefficient (D*) and vascular fraction (f) were evaluated. A multivariable model combing ADC, D, and f values using binary logistic regression analysis was built to diagnose endometrial fibrosis. Endometrial fibrosis patients demonstrated lower endometrial ADC, D, f values and ET (all p < 0.05). The multivariable model, ADC, D, f values and ET performed well in diagnosing endometrial fibrosis with AUC of 0.979, 0.965, 0.920, 0.901 and 0.833, respectively. The multivariable model revealed a better diagnostic accuracy than D, f and ET (all p < 0.05). Although ADC achieved a better diagnostic value than ET (z = 2.082, p < 0.05), no difference in AUC was shown among ADC, D, and f (all p > 0.05); between ET and D (p > 0.05); and between ET and f (p > 0.05). The reproducibility of ADC, D, f and D* values in patients with endometrial fibrosis and healthy women were good to excellent (ICC: 0.614–0.951). IVIM parameters exhibit promising potential to serve as imaging biomarkers in the noninvasive assessment of endometrial fibrosis.

Semi-Automated Segmentation of Bone Metastases from Whole-Body MRI: Reproducibility of Apparent Diffusion Coefficient Measurements.

Using semi-automated software simplifies quantitative analysis of the visible burden of disease on whole-body MRI diffusion-weighted images. To establish the intra- and inter-observer reproducibility of apparent diffusion coefficient (ADC) measures, we retrospectively analyzed data from 20 patients with bone metastases from breast (BCa; n = 10; aged 62.3 ± 14.8) or prostate cancer (PCa; n = 10; aged 67.4 ± 9.0) who had undergone examinations at two timepoints, before and after hormone-therapy. Four independent observers processed all images twice, first segmenting the entire skeleton on diffusion-weighted images, and then isolating bone metastases via ADC histogram thresholding (ADC: 650–1400 µm2/s). Dice Similarity, Bland-Altman method, and Intraclass Correlation Coefficient were used to assess reproducibility. Inter-observer Dice similarity was moderate (0.71) for women with BCa and poor (0.40) for men with PCa. Nonetheless, the limits of agreement of the mean ADC were just ±6% for women with BCa and ±10% for men with PCa (mean ADCs: 941 and 999 µm2/s, respectively). Inter-observer Intraclass Correlation Coefficients of the ADC histogram parameters were consistently greater in women with BCa than in men with PCa. While scope remains for improving consistency of the volume segmented, the observer-dependent variability measured in this study was appropriate to distinguish the clinically meaningful changes of ADC observed in patients responding to therapy, as changes of at least 25% are of interest.

Repeatability and reproducibility of apparent diffusion coefficient and fat fraction measurement of focal myeloma lesions on whole body magnetic resonance imaging.

Objective:To assess intra- and inter-reader variability of apparent diffusion coefficient (ADC) and fat fraction (FF) measurement in focal myeloma bone lesions and the influence of lesion size.Methods:22 myeloma patients with focal active disease on whole body MRI were included. Two readers outlined a small (5–10 mm) and large lesion (>10 mm) in each subject on derived ADC and FF maps; one reader performed this twice. Intra- and inter-reader agreement for small and large lesion groups were calculated for derived statistics from each map using within-subject standard deviation, coefficient of variation, interclass correlation coefficient measures, and visualized with Bland–Altman plots.Results:For mean ADC, intra- and inter-reader repeatability demonstrated equivalently low coefficient of variation (3.0–3.6%) and excellent interclass correlation coefficient (0.975–0.982) for both small and large lesions. For mean FF, intra- and inter-reader repeatability was significantly poorer for small lesions compared to large lesions (intra-reader within-subject standard variation estimate is 2.7 times higher for small lesions than large lesions (p = 0.0071), and for inter-reader variations is 3.8 times higher (p = 0.0070)).Conclusion:There is excellent intra- and inter-reader agreement for mean ADC estimates, even for lesions as small as 5 mm. For FF measurements, there is a significant increase in coefficient of variation for smaller lesions, suggesting lesions >10 mm should be selected for lesion FF measurement.Advances in knowledge:ADC measurements of focal myeloma have excellent intra- and inter-reader agreement. FF measurements are more susceptible to lesion size as intra- and inter-reader agreement is significantly impaired in lesions less than 10 mm.

Reproducibility of normalized apparent diffusion coefficient measurements on 3.0-T diffusion-weighted imaging of normal pancreas in a healthy population.

To prospectively compare the reproducibility of normal pancreas-normalized apparent diffusion coefficient (ADC) measurements for the normal pancreas and mean normalized ADCs at different pancreas anatomic locations.In total, 22 healthy volunteers underwent pancreatic 3.0-T magnetic resonance (MR) imaging, including axial diffusion-weighted (DW) imaging with 3 b values used (0, 400, and 800 s/mm2) and with the respiratory-triggered (RT) technique. The mean ADCs from 3 regions of interest (ROIs) in 5 anatomic locations (head [H], body [B], and tail [T] of pancreas and spleen [S] and erector spinae muscles [M]) were calculated. The pancreas-normalized ADC was defined as the ratio of the ADC for the pancreas to the ADC for the spleen or erector spinae muscle. Reproducibility of ADCs and normalized ADCs was assessed by the Bland–Altman method. The ADC and normalized ADC data were analyzed by repeated-measures ANOVA.Mean ADC and normalized ADC values did not differ (P >.05) with repeated measurements at the different pancreas anatomic locations. Reproducibility of pancreas-normalized ADC measurements in each of the 3 pancreatic anatomic locations was better with the erector spinae muscle rather than the spleen used as a reference. Mean ADC and normalized ADC values significantly differed between the 3 pancreatic segments (H: 1.36 × 10−3 mm2/s, B: 1.38 × 10−3 mm2/s, T: 1.25 × 10−3 mm2/s, P = .022; H/S: 1.75, B/S: 1.78, T/S: 1.59, P = .009; H/M: 0.91, B/M: 0.95, T/M: 0.85, P = .008). Mean ADC values and normalized ADC values showed a trend to decrease from the pancreatic head to tail.Our preliminary results suggest that normalized ADC measurements for the pancreas show good intra- and interobserver reproducibility, the erector spinae muscle is a better choice than the spleen for calculating normalized ADC values for the pancreas, and the normalized ADC values are lower for the pancreatic tail than other pancreatic segments.

Apparent diffusion coefficient reproducibility in brain tumors measured on 1.5 and 3 T clinical scanners: A pilot study

BackgroundGradient and coil systems, pulse sequence design, and imaging parameters, as well as different scanners, can influence apparent diffusion coefficient (ADC) values. The aim of this study was to evaluate the effect of two different field strengths on the reproducibility of mean absolute ADC measurements in various primary and secondary brain tumors. MethodsFifty patients with histologically proven brain tumors were prospectively examined on two MR scanners from the same vendor, with different field strengths—1.5T and 3T—on the same day. Absolute ADC values were compared using the Wilcoxon matched-pairs signed-rank test. Inter-scanner agreement between two different fields in the same tumor was examined using correlation coefficients, and the discrepancy between the highest and the lowest mean absolute ADC values between scanners was tested using a one-way analysis of variance. Statistical significance was set at p < 0.05. ResultsThere was no statistically significant difference between mean absolute ADC values obtained on 1.5T and 3T scanners for all patients and all brain tumor types. The intratumoral difference in ADC values, averaged from two scanners in the same tumor type, ranged from 1.58 to 4.5% for 1.5T, and from 1.18 to 4.37% for 3T.Inter-scanner agreement was high, and the kappa coefficient ranged from 0.88 to 0.99, with no significant difference between obtained values on different field strengths. ConclusionBased on the results obtained in our study, there is no significant difference between mean absolute ADC values measured in various primary and secondary brain tumors at different field strengths (1.5 and 3.0T MR systems), in the same patient, and in the same tumor, measured on the same day.

A data-driven statistical model that estimates measurement uncertainty improves interpretation of ADC reproducibility: a multi-site study of liver metastases

Apparent Diffusion Coefficient (ADC) is a potential quantitative imaging biomarker for tumour cell density and is widely used to detect early treatment changes in cancer therapy. We propose a strategy to improve confidence in the interpretation of measured changes in ADC using a data-driven model that describes sources of measurement error. Observed ADC is then standardised against this estimation of uncertainty for any given measurement. 20 patients were recruited prospectively and equitably across 4 sites, and scanned twice (test-retest) within 7 days. Repeatability measurements of defined regions (ROIs) of tumour and normal tissue were quantified as percentage change in mean ADC (test vs. re-test) and then standardised against an estimation of uncertainty. Multi-site reproducibility, (quantified as width of the 95% confidence bound between the lower confidence interval and higher confidence interval for all repeatability measurements), was compared before and after standardisation to the model. The 95% confidence interval width used to determine a statistically significant change reduced from 21.1 to 2.7% after standardisation. Small tumour volumes and respiratory motion were found to be important contributors to poor reproducibility. A look up chart has been provided for investigators who would like to estimate uncertainty from statistical error on individual ADC measurements.

Distortion-free diffusion MRI using an MRI-guided Tri-Cobalt 60 radiotherapy system: Sequence verification and preliminary clinical experience.

Monitoring tumor response during the course of treatment and adaptively modifying treatment plan based on tumor biological feedback may represent a new paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing and predicting tumor response to radiotherapy. However, the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) technique suffers from limited resolution, severe distortion, and possibly inaccurate ADC at low field strength. The purpose of this work was to develop a reliable, accurate and distortion-free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0.35 T MRI-guided radiotherapy system. A diffusion-prepared turbo spin echo readout (DP-TSE) sequence was developed and compared with the conventional diffusion-weighted single-shot echo-planar-imaging sequence on a 0.35 T MRI-guided radiotherapy system (ViewRay). A spatial integrity phantom was used to quantitate and compare the geometric accuracy of the two diffusion sequences for three orthogonal orientations. The apparent diffusion coefficient (ADC) accuracy was evaluated on a diffusion phantom under both 0 °C and room temperature to cover a diffusivity range between 0.40 × 10-3 and 2.10 × 10-3 mm2 /s. Ten room temperature measurements repeated on five different days were conducted to assess the ADC reproducibility of DP-TSE. Two glioblastoma (GBM) and six sarcoma patients were included to examine the in vivo feasibility. The target registration error (TRE) was calculated to quantitate the geometric accuracy where structural CT or MR images were co-registered to the diffusion images as references. ADC maps from DP-TSE and DW-ssEPI were calculated and compared. A tube phantom was placed next to patients not treated on ViewRay, and ADCs of this reference tube were also compared. The proposed DP-TSE passed the spatial integrity test (< 1 mm within 100 mm radius and < 2 mm within 175 mm radius) under the three orthogonal orientations. The detected errors were 0.474 ± 0.355 mm, 0.475 ± 0.287 mm, and 0.546 ± 0.336 mm in the axial, coronal, and sagittal plane. DW-ssEPI, however, failed the tests due to severe distortion and low signal intensity. Noise correction must be performed for the DW-ssEPI to avoid ADC quantitation errors, whereas it is optional for DP-TSE. At 0 °C, the two sequences provided accurate quantitation with < 3% variation with the reference. In the room temperature study, discrepancies between ADCs from DP-TSE and the reference were within 4%, but could be as high as 8% for DW-ssEPI after the noise correction. Excellent ADC reproducibility with a coefficient of variation < 5% was observed among the 10 measurements of DP-TSE, indicating desirable robustness for ADC-based tumor response assessment. In vivo TRE in DP-TSE was less than 1.6 mm overall, whereas it could be greater than 12 mm in DW-ssEPI. For GBM patients, the CSF and brain tissue ADCs from DP-TSE were within the ranges found in literature. ADC differences between the two techniques were within 8% among the six sarcoma patients. For the reference tube that had a relatively low diffusivity, the two diffusion sequences provided matched measurements. A diffusion technique with excellent geometric fidelity, accurate, and reproducible ADC measurement was demonstrated for longitudinal tumor response assessment using a low-field MRI-guided radiotherapy system.

Diffusion-weighted (DW) MRI in lung cancers: ADC test-retest repeatability.

To determine the test-retest repeatability of Apparent Diffusion Coefficient (ADC) measurements across institutions and MRI vendors, plus investigate the effect of post-processing methodology on measurement precision. Thirty malignant lung lesions >2cm in size (23 patients) were scanned on two occasions, using echo-planar-Diffusion-Weighted (DW)-MRI to derive whole-tumour ADC (b = 100, 500 and 800smm-2). Scanning was performed at 4 institutions (3 MRI vendors). Whole-tumour volumes-of-interest were copied from first visit onto second visit images and from one post-processing platform to an open-source platform, to assess ADC repeatability and cross-platform reproducibility. Whole-tumour ADC values ranged from 0.66-1.94x10-3mm2s-1 (mean = 1.14). Within-patient coefficient-of-variation (wCV) was 7.1% (95% CI 5.7-9.6%), limits-of-agreement (LoA) -18.0 to 21.9%. Lesions >3cm had improved repeatability: wCV 3.9% (95% CI 2.9-5.9%); and LoA -10.2 to 11.4%. Variability for lesions <3cm was 2.46 times higher. ADC reproducibility across different post-processing platforms was excellent: Pearson's R2 = 0.99; CoV 2.8% (95% CI 2.3-3.4%); and LoA -7.4 to 8.0%. A free-breathing DW-MRI protocol for imaging malignant lung tumours achieved satisfactory within-patient repeatability and was robust to changes in post-processing software, justifying its use in multi-centre trials. For response evaluation in individual patients, a change in ADC >21.9% will reflect treatment-related change. • In lung cancer, free-breathing DWI-MRI produces acceptable images with evaluable ADC measurement. • ADC repeatability coefficient-of-variation is 7.1% for lung tumours >2cm. • ADC repeatability coefficient-of-variation is 3.9% for lung tumours >3cm. • ADC measurement precision is unaffected by the post-processing software used. • In multicentre trials, 22% increase in ADC indicates positive treatment response.