Quantification of intramuscular fat in patients with late-onset Pompe disease by conventional magnetic resonance imaging for the long-term follow-up of enzyme replacement therapy

OBJECTIVE: The objective of this study was to evaluate a quantitative method based on conventional T1-weighted magnetic resonance (MR) imaging to assess fatty muscular degeneration in patients with late-onset Pompe disease and to compare it with semi-quantitative visual evaluation (the Mercuri score). In addition, a long-term retrospective data analysis was performed to evaluate treatment response to enzyme replacement therapy with alglucosidase alfa. METHODS: MR images of the lumbar spine were acquired in 41 patients diagnosed with late-onset Pompe disease from 2006 through 2015. Two independent readers retrospectively evaluated fatty degeneration of the psoas and paraspinal muscles by applying the Mercuri score. Quantitative semi-automated muscle and fat tissue separation was performed, and inter-observer agreement and correlations with clinical parameters were assessed. Follow-up examinations were performed in 13 patients treated with alglucosidase alfa after a median of 39 months; in 7/13 patients, an additional follow-up examination was completed after a median of 63 months. RESULTS: Inter-observer agreement was high. Measurements derived from the quantitative method correlated well with Medical Research Council scores of muscle strength, with moderate correlations found for the 6-minute walk test, the 4-step stair climb test, and spirometry in the supine position. A significant increase in the MR-derived fat fraction of the psoas muscle was found between baseline and follow-up 1 (P = 0.016), as was a significant decrease in the performance on the 6-minute walk test (P = 0.006) and 4-step stair climb test (P = 0.034), as well as plasma creatine kinase (P = 0.016). No statistically significant difference in clinical or MR-derived parameters was found between follow-up 1 and follow-up 2. CONCLUSIONS: Quantification of fatty muscle degeneration using the semi-automated method can provide a more detailed overview of disease progression than semi-quantitative Mercuri scoring. MR-derived data correlated with clinical symptoms and patient exercise capacity. After an initial worsening, the fat fraction of the psoas muscle and performance on the 6-minute walk test stayed constant during long-term follow-up under enzyme replacement therapy

Benchmarking Wilms' tumor in multisequence MRI data: why does current clinical practice fail? Which popular segmentation algorithms perform well?

Wilms' tumor is one of the most frequent malignant solid tumors in childhood. Accurate segmentation of tumor tissue is a key step during therapy and treatment planning. Since it is difficult to obtain a comprehensive set of tumor data of children, there is no benchmark so far allowing evaluation of the quality of human or computer-based segmentations. The contributions in our paper are threefold: (i) we present the first heterogeneous Wilms' tumor benchmark data set. It contains multisequence MRI data sets before and after chemotherapy, along with ground truth annotation, approximated based on the consensus of five human experts. (ii) We analyze human expert annotations and interrater variability, finding that the current clinical practice of determining tumor volume is inaccurate and that manual annotations after chemotherapy may differ substantially. (iii) We evaluate six computer-based segmentation methods, ranging from classical approaches to recent deep-learning techniques. We show that the best ones offer a quality comparable to human expert annotations

Quantification of intramuscular fat in patients with late-onset Pompe disease by conventional magnetic resonance imaging for the long-term follow-up of enzyme replacement therapy

OBJECTIVE The objective of this study was to evaluate a quantitative method based on conventional T1-weighted magnetic resonance (MR) imaging to assess fatty muscular degeneration in patients with late-onset Pompe disease and to compare it with semi-quantitative visual evaluation (the Mercuri score). In addition, a long-term retrospective data analysis was performed to evaluate treatment response to enzyme replacement therapy with alglucosidase alfa. METHODS MR images of the lumbar spine were acquired in 41 patients diagnosed with late-onset Pompe disease from 2006 through 2015. Two independent readers retrospectively evaluated fatty degeneration of the psoas and paraspinal muscles by applying the Mercuri score. Quantitative semi-automated muscle and fat tissue separation was performed, and inter-observer agreement and correlations with clinical parameters were assessed. Follow-up examinations were performed in 13 patients treated with alglucosidase alfa after a median of 39 months; in 7/13 patients, an additional follow-up examination was completed after a median of 63 months. RESULTS Inter-observer agreement was high. Measurements derived from the quantitative method correlated well with Medical Research Council scores of muscle strength, with moderate correlations found for the 6-minute walk test, the 4-step stair climb test, and spirometry in the supine position. A significant increase in the MR-derived fat fraction of the psoas muscle was found between baseline and follow-up 1 (P = 0.016), as was a significant decrease in the performance on the 6-minute walk test (P = 0.006) and 4-step stair climb test (P = 0.034), as well as plasma creatine kinase (P = 0.016). No statistically significant difference in clinical or MR-derived parameters was found between follow-up 1 and follow-up 2. CONCLUSIONS Quantification of fatty muscle degeneration using the semi-automated method can provide a more detailed overview of disease progression than semi-quantitative Mercuri scoring. MR-derived data correlated with clinical symptoms and patient exercise capacity. After an initial worsening, the fat fraction of the psoas muscle and performance on the 6-minute walk test stayed constant during long-term follow-up under enzyme replacement therapy

Diffusion-weighted MRI and histogram analysis: assessment of response to neoadjuvant chemotherapy in nephroblastoma

PURPOSE To assess the value of diffusion-weighted MRI (DW-MRI) in the non-invasive prediction of blastemal remnant after neoadjuvant chemotherapy in nephroblastoma. METHODS This IRB-approved study included 32 pediatric patients with 35 tumors who underwent DW-MRI prior and after completion of neoadjuvant chemotherapy and subsequent surgical resection. Two blinded radiologists volumetrically assessed each tumor on pre- and post-neoadjuvant images and the parameters mean ADC, median ADC, 12.5th/25th/75th ADC percentile, skewness, and kurtosis were calculated. Blastemal remnant was determined per the pathology report. Associations between imaging features and blastemal remnant quartiles were examined using the Kruskal-Wallis test and adjusted for false discovery rate. RESULTS Inter-reader agreement was high for mean ADC, skewness, kurtosis, and volume (ICC: 0.76-0.998). Pre-therapeutic histogram parameters skewness and kurtosis were found to be higher in patients with a higher amount of blastemal remnant for reader 1 (overall p = 0.035) and for kurtosis in reader 2 (overall p = 0.032) with skewness not reaching the level of statistical significance (overall p = 0.055). Higher tumor volume on pre-treatment imaging was associated with a higher amount of blastemal remnant after therapy (overall p = 0.032 for both readers). CONCLUSIONS Pre-treatment skewness and kurtosis of ADC histogram analysis were significantly associated with a larger fraction of a blastemal remnant after neoadjuvant chemotherapy. These findings could be incorporated into a more personalized chemotherapeutic regime in these patients and offer prognostic information at the time of initial diagnosis

Diffusion-weighted MRI in the assessment of nephroblastoma: results of a multi-center trial

PURPOSE To assess the value of diffusion-weighted MRI in the pre-therapeutic evaluation of pediatric renal cortical tumors. METHODS This IRB-approved, retrospective multi-center study included 122 pediatric patients with 130 renal tumors, who underwent MRI including DWI before neoadjuvant chemotherapy and nephrectomy. Two radiologists independently assessed each tumor volumetrically, and apparent diffusion coefficient (ADC) values were calculated on a voxel-wise basis, including parameters derived from histogram and texture analysis. RESULTS Inter-reader agreement was excellent (ICC 0.717-0.975). For both readers, patients with locally aggressive tumor growth (SIOP 3 stage) or with metastases (M1) had significantly lower 12.5th-percentile ADC values (p ≤ 0.028) compared to those with lower-stage tumors, and the parameter energy differed significantly between patients with M1 and those with M0 status (p ≤ 0.028). Contrast and homogeneity differed significantly between benign nephroblastomatosis and malignant nephroblastoma (p ≤ 0.045, both readers). As compared to all other subtypes, the blastemal subtype demonstrated significantly higher skewness (p ≤ 0.022, both readers) and the diffuse anaplastic subtype demonstrated significantly higher 75th-percentile ADC values (p ≤ 0.042, both readers). CONCLUSIONS Diffusion-weighted MRI may be of value in identifying benign nephroblastomatosis and assessing nephroblastoma subtypes. Therefore, further research is warranted to assess its value in risk stratification for pediatric patients with renal tumors in the future

Fat fraction of the paraspinal muscles during follow-up.

<p>Images acquired at baseline (panel a), followed-up yearly (panel b-f) are shown. Fatty infiltrated muscle is colored red. The fat fraction increased from 0.38 (panel a) via 0.46 (b), 0.53 (c), 0.57 (d), 0.66 (e) to 0.74 (f).</p

Inter-observer agreement concerning quantitative MR-derived data.

<p>Inter-observer agreement concerning quantitative MR-derived data.</p

Correlations between MR-derived data and clinical parameters.

<p>Correlations between MR-derived data and clinical parameters.</p

MR-derived measurement of the fat fraction.

<p>A region of interest is selected from a T1-weighted TSE sequence in the left paraspinal musculature at the L3-level (panel a). Fat fraction is calculated using the equation FF = 1 –FCSA/CSA; a signal intensity threshold of 772 (derived from normal muscle–the medial multifidus muscle in this case) segregates muscle from fat tissue. Pixels beneath this threshold, colored red (panel b), constitute the FCSA (1096 mm²), while the entire area of the ROI constitutes the CSA (1466 mm²). These data result in an FF value of 0.25.</p