Accuracy of 3D real-time MRI temperature mapping in gel phantoms during microwave heating.

BACKGROUND: Interventional magnetic resonance imaging (MRI) can provide a comprehensive setting for microwave ablation of tumors with real-time monitoring of the energy delivery using MRI-based temperature mapping. The purpose of this study was to quantify the accuracy of three-dimensional (3D) real-time MRI temperature mapping during microwave heating in vitro by comparing MRI thermometry data to reference data measured by fiber-optical thermometry. METHODS: Nine phantom experiments were evaluated in agar-based gel phantoms using an in-room MR-conditional microwave system and MRI thermometry. MRI measurements were performed for 700 s (25 slices; temporal resolution 2 s). The temperature was monitored with two fiber-optical temperature sensors approximately 5 mm and 10 mm distant from the microwave antenna. Temperature curves of the sensors were compared to MRI temperature data of single-voxel regions of interest (ROIs) at the sensor tips; the accuracy of MRI thermometry was assessed as the root-mean-squared (RMS)-averaged temperature difference. Eighteen neighboring voxels around the original ROI were also evaluated and the voxel with the smallest temperature difference was additionally selected for further evaluation. RESULTS: The maximum temperature changes measured by the fiber-optical sensors ranged from 7.3 K to 50.7 K. The median RMS-averaged temperature differences in the originally selected voxels ranged from 1.4 K to 3.4 K. When evaluating the minimum-difference voxel from the neighborhood, the temperature differences ranged from 0.5 K to 0.9 K. The microwave antenna and the MRI-conditional in-room microwave generator did not induce relevant radiofrequency artifacts. CONCLUSION: Accurate 3D real-time MRI temperature mapping during microwave heating with very low RMS-averaged temperature errors below 1 K is feasible in gel phantoms. RELEVANCE STATEMENT: Accurate MRI-based volumetric real-time monitoring of temperature distribution and thermal dose is highly relevant in clinical MRI-based interventions and can be expected to improve local tumor control, as well as procedural safety by extending the limits of thermal (e.g., microwave) ablation of tumors in the liver and in other organs. KEY POINTS: Interventional MRI can provide a comprehensive setting for the microwave ablation of tumors. MRI can monitor the microwave ablation using real-time MRI-based temperature mapping. 3D real-time MRI temperature mapping during microwave heating is feasible. Measured temperature errors were below 1 °C in gel phantoms. The active in-room microwave generator did not induce any relevant radiofrequency artifacts.

Repeatability quantification of brain diffusion-weighted imaging for future clinical implementation at a low-field MR-linac.

BACKGROUND: Longitudinal assessments of apparent diffusion coefficients (ADCs) derived from diffusion-weighted imaging (DWI) during intracranial radiotherapy at magnetic resonance imaging-guided linear accelerators (MR-linacs) could enable early response assessment by tracking tumor diffusivity changes. However, DWI pulse sequences are currently unavailable in clinical practice at low-field MR-linacs. Quantifying the in vivo repeatability of ADC measurements is a crucial step towards clinical implementation of DWI sequences but has not yet been reported on for low-field MR-linacs. This study assessed ADC measurement repeatability in a phantom and in vivo at a 0.35 T MR-linac. METHODS: Eleven volunteers and a diffusion phantom were imaged on a 0.35 T MR-linac. Two echo-planar imaging DWI sequence variants, emphasizing high spatial resolution ("highRes") and signal-to-noise ratio ("highSNR"), were investigated. A test-retest study with an intermediate outside-scanner-break was performed to assess repeatability in the phantom and volunteers' brains. Mean ADCs within phantom vials, cerebrospinal fluid (CSF), and four brain tissue regions were compared to literature values. Absolute relative differences of mean ADCs in pre- and post-break scans were calculated for the diffusion phantom, and repeatability coefficients (RC) and relative RC (relRC) with 95% confidence intervals were determined for each region-of-interest (ROI) in volunteers. RESULTS: Both DWI sequence variants demonstrated high repeatability, with absolute relative deviations below 1% for water, dimethyl sulfoxide, and polyethylene glycol in the diffusion phantom. RelRCs were 7% [5%, 12%] (CSF; highRes), 12% [9%, 22%] (CSF; highSNR), 9% [8%, 12%] (brain tissue ROIs; highRes), and 6% [5%, 7%] (brain tissue ROIs; highSNR), respectively. ADCs measured with the highSNR variant were consistent with literature values for volunteers, while smaller mean values were measured for the diffusion phantom. Conversely, the highRes variant underestimated ADCs compared to literature values, indicating systematic deviations. CONCLUSIONS: High repeatability of ADC measurements in a diffusion phantom and volunteers' brains were measured at a low-field MR-linac. The highSNR variant outperformed the highRes variant in accuracy and repeatability, at the expense of an approximately doubled voxel volume. The observed high in vivo repeatability confirms the potential utility of DWI at low-field MR-linacs for early treatment response assessment.

Clinical benefits of MRI-guided freehand biopsy of small focal liver lesions in comparison to CT guidance.

OBJECTIVES: To compare clinical success, procedure time, and complication rates between MRI-guided and CT-guided real-time biopsies of small focal liver lesions (FLL) < 20 mm. METHODS: A comparison of a prospectively collected MRI-guided cohort (n = 30) to a retrospectively collected CT-guided cohort (n = 147) was performed, in which patients underwent real-time biopsies of small FLL < 20 mm in a freehand technique. In both groups, clinical and periprocedural data, including clinical success, procedure time, and complication rates (classified according to CIRSE guidelines), were analyzed. Wilcoxon rank sum test, Pearson's chi-squared test, and Fisher's exact test were used for statistical analysis. Additionally, propensity score matching (PSM) was performed using the following criteria for direct matching: age, gender, presence of liver cirrhosis, liver lobe, lesion diameter, and skin-to-target distance. RESULTS: The median FLL diameter in the MRI-guided cohort was significantly smaller compared to CT guidance (p < 0.001; 11.0 mm vs. 16.3 mm), while the skin-to-target distance was significantly longer (p < 0.001; 90.0 mm vs. 74.0 mm). MRI-guided procedures revealed significantly higher clinical success compared to CT guidance (p = 0.021; 97% vs. 79%) as well as lower complication rates (p = 0.047; 0% vs. 13%). Total procedure time was significantly longer in the MRI-guided cohort (p < 0.001; 38 min vs. 28 min). After PSM (n = 24/n = 38), MRI-guided procedures still revealed significantly higher clinical success compared to CT guidance (p = 0.039; 96% vs. 74%). CONCLUSION: Despite the longer procedure time, freehand biopsy of small FLL < 20 mm under MR guidance can be considered superior to CT guidance because of its high clinical success and low complication rates. CLINICAL RELEVANCE STATEMENT: Biopsy of small liver lesions is challenging due to the size and conspicuity of the lesions on native images. MRI offers higher soft tissue contrast, which translates into a higher success of obtaining enough tissue material with MRI compared to CT-guided biopsies. KEY POINTS: • Image-guided biopsy of small focal liver lesions (FLL) is challenging due to inadequate visualization, leading to sampling errors and false-negative biopsies. • MRI-guided real-time biopsy of FLL < 20 mm revealed significantly higher clinical success (p = 0.021; 97% vs. 79%) and lower complication rates (p = 0.047; 0% vs. 13%) compared to CT guidance. • Although the procedure time is longer, MRI-guided biopsy can be considered superior for small FLL < 20 mm.

Investigations on correlations between changes of optical tissue properties and NMR relaxation times.

BACKGROUND: Accurate light dosimetry is a complex remaining challenge in interstitial photodynamic therapy (iPDT) for malignant gliomas. The light dosimetry should ideally be based on the tissue morphology and the individual optical tissue properties of each tissue type in the target region. First investigations are reported on using NMR information to estimate changes of individual optical tissue properties. METHODS: Porcine brain tissue and optical tissue phantoms were investigated. To the porcine brain, supplements were added to simulate an edema or high blood content. The tissue phantoms were based on agar, Lipoveneous, ink, blood and gadobutrol (Gd-based MRI contrast agent). The concentrations of phantom ingredients and tissue additives are varied to compare concentration-dependent effects on optical and NMR properties. A 3-tesla whole-body MRI system was used to determine T1 and T2 relaxation times. Optical tissue properties, i.e., the spectrally resolved absorption and reduced scattering coefficient, were obtained using a single integrating sphere setup. The observed changes of NMR and optical properties were compared to each other. RESULTS: By adjusting the NMR relaxation times and optical tissue properties of the tissue phantoms to literature values, recipes for human brain tumor, white matter and grey matter tissue phantoms were obtained that mimic these brain tissues simultaneously in both properties. For porcine brain tissue, it was observed that with increasing water concentration in the tissue, both NMR-relaxation times increased, while µa decreased and µs' increased at 635 nm. The addition of blood to porcine brain samples showed a constant T1, while T2 shortened and the absorption coefficient at 635 nm increased. CONCLUSIONS: In this investigation, by changing sample contents, notable changes of both NMR relaxation times and optical tissue properties have been observed and their relations examined. The developed dual NMR/optical tissue phantoms can be used in iPDT research, clinical training and demonstrations.

Applications of Diffusion-Weighted MRI to the Musculoskeletal System.

Diffusion-weighted imaging (DWI) is an established MRI technique that can investigate tissue microstructure at the scale of a few micrometers. Musculoskeletal tissues typically have a highly ordered structure to fulfill their functions and therefore represent an optimal application of DWI. Even more since disruption of tissue organization affects its biomechanical properties and may indicate irreversible damage. The application of DWI to the musculoskeletal system faces application-specific challenges on data acquisition including susceptibility effects, the low T2 relaxation time of most musculoskeletal tissues (2-70 msec) and the need for sub-millimetric resolution. Thus, musculoskeletal applications have been an area of development of new DWI methods. In this review, we provide an overview of the technical aspects of DWI acquisition including diffusion-weighting, MRI pulse sequences and different diffusion regimes to study tissue microstructure. For each tissue type (growth plate, articular cartilage, muscle, bone marrow, intervertebral discs, ligaments, tendons, menisci, and synovium), the rationale for the use of DWI and clinical studies in support of its use as a biomarker are presented. The review describes studies showing that DTI of the growth plate has predictive value for child growth and that DTI of articular cartilage has potential to predict the radiographic progression of joint damage in early stages of osteoarthritis. DTI has been used extensively in skeletal muscle where it has shown potential to detect microstructural and functional changes in a wide range of muscle pathologies. DWI of bone marrow showed to be a valuable tool for the diagnosis of benign and malignant acute vertebral fractures and bone metastases. DTI and diffusion kurtosis have been investigated as markers of early intervertebral disc degeneration and lower back pain. Finally, promising new applications of DTI to anterior cruciate ligament grafts and synovium are presented. The review ends with an overview of the use of DWI in clinical routine. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.

Automated MRI Lung Segmentation and 3D Morphologic Features for Quantification of Neonatal Lung Disease.

Purpose: To analyze the performance of deep learning (DL) models for segmentation of the neonatal lung in MRI and investigate the use of automated MRI-based features for assessment of neonatal lung disease. Materials and Methods: Quiet-breathing MRI was prospectively performed in two independent cohorts of preterm infants (median gestational age, 26.57 weeks; IQR, 25.3-28.6 weeks; 55 female and 48 male infants) with (n = 86) and without (n = 21) chronic lung disease (bronchopulmonary dysplasia [BPD]). Convolutional neural networks were developed for lung segmentation, and a three-dimensional reconstruction was used to calculate MRI features for lung volume, shape, pixel intensity, and surface. These features were explored as indicators of BPD and disease-associated lung structural remodeling through correlation with lung injury scores and multinomial models for BPD severity stratification. Results: The lung segmentation model reached a volumetric Dice coefficient of 0.908 in cross-validation and 0.880 on the independent test dataset, matching expert-level performance across disease grades. MRI lung features demonstrated significant correlations with lung injury scores and added structural information for the separation of neonates with BPD (BPD vs no BPD: average area under the receiver operating characteristic curve [AUC], 0.92 ± 0.02 [SD]; no or mild BPD vs moderate or severe BPD: average AUC, 0.84 ± 0.03). Conclusion: This study demonstrated high performance of DL models for MRI neonatal lung segmentation and showed the potential of automated MRI features for diagnostic assessment of neonatal lung disease while avoiding radiation exposure.Keywords: Bronchopulmonary Dysplasia, Chronic Lung Disease, Preterm Infant, Lung Segmentation, Lung MRI, BPD Severity Assessment, Deep Learning, Lung Imaging Biomarkers, Lung Topology Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by Parraga and Sharma in this issue.

MRI pulmonary artery flow detects lung vascular pathology in preterms with lung disease.

BACKGROUND: Pulmonary vascular disease (PVD) affects the majority of preterm neonates with bronchopulmonary dysplasia (BPD) and significantly determines long-term mortality through undetected progression into pulmonary hypertension. Our objectives were to associate characteristics of pulmonary artery (PA) flow and cardiac function with BPD-associated PVD near term using advanced magnetic resonance imaging (MRI) for improved risk stratification. METHODS: Preterms <32 weeks postmenstrual age (PMA) with/without BPD were clinically monitored including standard echocardiography and prospectively enrolled for 3 T MRI in spontaneous sleep near term (AIRR (Attention to Infants at Respiratory Risks) study). Semi-manual PA flow quantification (phase-contrast MRI; no BPD n=28, mild BPD n=35 and moderate/severe BPD n=25) was complemented by cardiac function assessment (cine MRI). RESULTS: We identified abnormalities in PA flow and cardiac function, i.e. increased net forward volume right/left ratio, decreased mean relative area change and pathological right end-diastolic volume, to sensitively detect BPD-associated PVD while correcting for PMA (leave-one-out area under the curve 0.88, sensitivity 0.80 and specificity 0.81). We linked these changes to increased right ventricular (RV) afterload (RV-arterial coupling (p=0.02), PA mid-systolic notching (t2; p=0.015) and cardiac index (p=1.67×10-8)) and correlated echocardiographic findings. Identified in moderate/severe BPD, we successfully applied the PA flow model in heterogeneous mild BPD cases, demonstrating strong correlation of PVD probability with indicators of BPD severity, i.e. duration of mechanical ventilation (rs=0.63, p=2.20×10-4) and oxygen supplementation (rs=0.60, p=6.00×10-4). CONCLUSIONS: Abnormalities in MRI PA flow and cardiac function exhibit significant, synergistic potential to detect BPD-associated PVD, advancing the possibilities of risk-adapted monitoring.

Optimized visualization of focal liver lesions and vascular structures in real-time T1-weighted gradient echo sequences for magnetic resonance-guided liver procedures.

PURPOSE: This study aimed to determine the optimal sequence parameters of a real-time T1-weighted (T1w) gradient echo (GRE) sequence for magnetic resonance (MR)-guided liver interventions. METHODS: We included 94 patients who underwent diagnostic liver MR imaging (MRI) and acquired additional real-time T1w GRE sequences with a closed 1.5-T MRI scanner 20 min after a liver-specific contrast agent was injected. In four measurement series, one of the following four sequence parameters was changed, and repeated scans with different values for this parameter were acquired: flip angle (FA) (10-90°), repetition time (TR) (5.47-8.58 ms), bandwidth (BW) (300-700 Hz/pixel), and matrix (96 × 96-256 × 256). Two readers rated the visualizations of the target and risk structures (7-point Likert scale) and the extent of artifacts (6-point Likert scale); they also quantified the lesion-liver contrast ratio, the lesion-liver contrast-to-noise ratio (CNR), and the liver signal-to-noise ratio (SNR). Substratification analyses were performed for differences in overall visual and quantitative assessments depending on the lesion size, type, and the presence of cirrhosis. RESULTS: For the utilized FAs and matrix sizes, significant differences were found in the visual assessments of the conspicuity of target lesions, risk structures, and the extent of artifacts as well as in the quantitative assessments of lesion-liver contrast ratios and liver SNRs (all P < 0.001). No differences were observed for modified TR and BW. Significantly increased conspicuity of the target and vascular structures was observed for both higher FAs and matrix sizes, while the ghosting artifacts increased and decreased, respectively. For primary liver tumors compared with metastatic lesions, and for cirrhotic livers compared with normal liver parenchyma, significantly decreased conspicuity of the target lesions (P = 0.005, P = 0.005), lesion-liver CNRs (P = 0.005, P = 0.032), and lesion-liver contrast ratios (P = 0.015, P = 0.032) were found. All results showed no significant correlation with lesion size. CONCLUSION: We recommend an FA of 30°-45° and a matrix size of 128 × 128-192 × 192 for MR-guided liver interventions with real-time T1w sequences to provide a balance between good visualizations of target and risk structures, high signal intensities, and low ghosting artifacts. The visualization of the target lesion may vary due to clinical conditions, such as lesion type or associated chronic liver disease.

Magnetic resonance imaging-based scoring of the diseased lung in the preterm infant with bronchopulmonary dysplasia: UNiforme Scoring of the disEAsed Lung in BPD (UNSEAL BPD).

Neonatal chronic lung disease lacks standardized assessment of lung structural changes. We addressed this clinical need by the development of a novel scoring system [UNSEAL BPD (UNiforme Scoring of the disEAsed Lung in BPD)] using T2-weighted single-shot fast-spin-echo sequences from 3 T MRI in very premature infants with and without bronchopulmonary dysplasia (BPD). Quantification of interstitial and airway remodeling, emphysematous changes, and ventilation inhomogeneity was achieved by consensus scoring on a five-point Likert scale. We successfully identified moderate and severe disease by logistic regression [area under the curve (AUC), 0.89] complemented by classification tree analysis revealing gestational age-specific structural changes. We demonstrated substantial interreader reproducibility (weighted Cohen's κ 0.69) and disease specificity (AUC = 0.91). Our novel MRI score enables the standardized assessment of disease-characteristic structural changes in the preterm lung exhibiting significant potential as a quantifiable endpoint in early intervention clinical trials and long-term disease monitoring.

Associations of gestational diabetes and proton density fat fraction of vertebral bone marrow and paraspinal musculature in premenopausal women.

Background and objective: Fat content in bones and muscles, quantified by magnetic resonance imaging (MRI) as a proton density fat fraction (PDFF) value, is an emerging non-invasive biomarker. PDFF has been proposed to indicate bone and metabolic health among postmenopausal women. Premenopausal women with a history of gestational diabetes (GDM) carry an increased risk of developing type 2 diabetes and an increased risk of fractures. However, no studies have investigated the associations between a history of GDM and PDFF of bone or of paraspinal musculature (PSM), composed of autochthonous muscle (AM) and psoas muscle, which are responsible for moving and stabilizing the spine. This study aims to investigate whether PDFF of vertebral bone marrow and of PSM are associated with a history of GDM in premenopausal women. Methods: A total of 37 women (mean age 36.3 ± 3.8 years) who were 6 to 15 months postpartum with (n=19) and without (n=18) a history of GDM underwent whole-body 3T MRI, including a chemical shift encoding-based water-fat separation. The PDFF maps were calculated for the vertebral bodies and PSM. The cross-sectional area (CSA) of PSM was obtained. Associations between a history of GDM and PDFF were assessed using multivariable linear and logistic regression models. Results: The PDFF of the vertebral bodies was significantly higher in women with a history of GDM (GDM group) than in women without (thoracic: median 41.55 (interquartile range 32.21-49.48)% vs. 31.75 (30.03-34.97)%; p=0.02, lumbar: 47.84 (39.19-57.58)% vs. 36.93 (33.36-41.31)%; p=0.02). The results remained significant after adjustment for age and body mass index (BMI) (p=0.01-0.02). The receiver operating characteristic curves showed optimal thoracic and lumbar vertebral PDFF cutoffs at 38.10% and 44.18%, respectively, to differentiate GDM (AUC 0.72 and 0.73, respectively, sensitivity 0.58, specificity 0.89). The PDFF of the AM was significantly higher in the GDM group (12.99 (12.18-15.90)% vs. 10.83 (9.39-14.71)%; p=0.04) without adjustments, while the CSA was similar between the groups (p=0.34). Conclusion: A history of GDM is significantly associated with a higher PDFF of the vertebral bone marrow, independent of age and BMI. This statistical association between GDM and increased PDFF highlights vertebral bone marrow PDFF as a potential biomarker for the assessment of bone health in premenopausal women at risk of diabetes.

Evaluation of an anthropomorphic ion chamber and 3D gel dosimetry head phantom at a 0.35 T MR-linac using separate 1.5 T MR-scanners for gel readout.

PURPOSE: To date, no universally accepted technique for the evaluation of the overall dosimetric performance of hybrid integrated magnetic resonance imaging (MR) - linear accelerators (linacs) is available. We report on the suitability and reliability of a novel phantom with modular inserts for combined polymer gel (PG) and ionisation chamber (IC) measurements at a 0.35 T MR-linac. METHODS: Three 3D-printed, modular head phantoms, based on real patient anatomy, were used for repeated (2 times) PG irradiations of cranial treatment plans on a 0.35 T MR-linac. The PG readout was performed on two 1.5 T diagnostic MR-scanners to reduce scanning time. The PG dose volumes were normalised to the IC dose (normalised dose N1) and to the median planning target volume dose (normalised dose N2). Linearity of the PG dose response was validated and dose profiles, centres of mass (COM) of the 95% isodoses and dose volume histograms (DVH) were compared between planned and measured dose distributions and a 3D gamma analysis was performed. RESULTS: Dose linearity of the PG was good (R2> 0.99 for all linear fit functions). High agreement was found between planned and measured dose volumes in the dose profiles and DVHs. The largest dose deviation was found in the intermediate dose region (mean dose deviation 0.2Gy; 5.6%). A mean COM offset of 1.2mm indicated high spatial accuracy. Mean 3D gamma passing rates (2%, 2mm) of 83.3% for N1 and 91.6% for N2 dose distributions were determined. When comparing repeated PG measurements to each other, a mean gamma passing rate of 95.7% was found. CONCLUSION: The new modular phantom was found practical for use at a 0.35 T MR-linac. In contrast to the high dose region, larger mean deviations were found in the mid dose range. The PG measurements showed high reproducibility. The MR-linac performed well in a non-adaptive setting in terms of spatial and dosimetric accuracy.

Artifact reduction of coaxial needles in magnetic resonance imaging-guided abdominal interventions at 1.5 T: a phantom study.

Needle artifacts pose a major limitation for MRI-guided interventions, as they impact the visually perceived needle size and needle-to-target-distance. The objective of this agar liver phantom study was to establish an experimental basis to understand and reduce needle artifact formation during MRI-guided abdominal interventions. Using a vendor-specific prototype fluoroscopic T1-weighted gradient echo sequence with real-time multiplanar acquisition at 1.5 T, the influence of 6 parameters (flip angle, bandwidth, matrix, slice thickness, read-out direction, intervention angle relative to B0) on artifact formation of 4 different coaxial MR-compatible coaxial needles (Nitinol, 16G-22G) was investigated. As one parameter was modified, the others remained constant. For each individual parameter variation, 2 independent and blinded readers rated artifact diameters at 2 predefined positions (15 mm distance from the perceived needle tip and at 50% of the needle length). Differences between the experimental subgroups were assessed by Bonferroni-corrected non-parametric tests. Correlations between continuous variables were expressed by the Bravais-Pearson coefficient and interrater reliability was quantified using the intraclass classification coefficient. Needle artifact size increased gradually with increasing flip angles (p = 0.002) as well as increasing intervention angles (p < 0.001). Artifact diameters differed significantly between the chosen matrix sizes (p = 0.002) while modifying bandwidth, readout direction, and slice thickness showed no significant differences. Interrater reliability was high (intraclass correlation coefficient 0.776-0.910). To minimize needle artifacts in MRI-guided abdominal interventions while maintaining optimal visibility of the coaxial needle, we suggest medium-range flip angles and low intervention angles relative to B0.

Measurement-based range evaluation for quality assurance of CBCT-based dose calculations in adaptive proton therapy.

PURPOSE: The implementation of volumetric in-room imaging for online adaptive radiotherapy makes extensive testing of this image data for treatment planning necessary. Especially for proton beams the higher sensitivity to stopping power properties of the tissue results in more stringent requirements. Current approaches mainly focus on recalculation of the plans on the new image data, lacking experimental verification, and ignoring the impact on the plan re-optimization process. The aim of this study was to use gel and film dosimetry coupled with a three-dimensional (3D) printed head phantom (based on the planning CT of the patient) for 3D range verification of intensity-corrected cone beam computed tomography (CBCT) image data for adaptive proton therapy. METHODS: Single field uniform dose pencil beam scanning proton plans were optimized for three different patients on the patients' planning CT (planCT) and the patients' intensity-corrected CBCT (scCBCT) for the same target volume using the same optimization constraints. The CBCTs were corrected on projection level using the planCT as a prior. The dose optimized on planCT and recalculated on scCBCT was compared in terms of proton range differences (80% distal fall-off, recalculation). Moreover, the dose distribution resulting from recalculation of the scCBCT-optimized plan on the planCT and the original planCT dose distribution were compared (simulation). Finally, the two plans of each patient were irradiated on the corresponding patient-specific 3D printed head phantom using gel dosimetry inserts for one patient and film dosimetry for all three patients. Range differences were extracted from the measured dose distributions. The measured and the simulated range differences were corrected for range differences originating from the initial plans and evaluated. RESULTS: The simulation approach showed high agreement with the standard recalculation approach. The median values of the range differences of these two methods agreed within 0.1 mm and the interquartile ranges (IQRs) within 0.3 mm for all three patients. The range differences of the film measurement were accurately matching with the simulation approach in the film plane. The median values of these range differences deviated less than 0.1 mm and the IQRs less than 0.4 mm. For the full 3D evaluation of the gel range differences, the median value and IQR matched those of the simulation approach within 0.7 and 0.5 mm, respectively. scCBCT- and planCT-based dose distributions were found to have a range agreement better than 3 mm (median and IQR) for all considered scenarios (recalculation, simulation, and measurement). CONCLUSIONS: The results of this initial study indicate that an online adaptive proton workflow based on scatter-corrected CBCT image data for head irradiations is feasible. The novel presented measurement- and simulation-based method was shown to be equivalent to the standard literature recalculation approach. Additionally, it has the capability to catch effects of image differences on the treatment plan optimization. This makes the measurement-based approach particularly interesting for quality assurance of CBCT-based online adaptive proton therapy. The observed uncertainties could be kept within those of the registration and positioning. The proposed validation could also be applied for other alternative in-room images, e.g. for MR-based pseudoCTs.

Analyzing the co-localization of substantia nigra hyper-echogenicities and iron accumulation in Parkinson's disease: A multi-modal atlas study with transcranial ultrasound and MRI.

BACKGROUND: Transcranial B-mode sonography (TCS) can detect hyperechogenic speckles in the area of the substantia nigra (SN) in Parkinson's disease (PD). These speckles correlate with iron accumulation in the SN tissue, but an exact volumetric localization in and around the SN is still unknown. Areas of increased iron content in brain tissue can be detected in vivo with magnetic resonance imaging, using quantitative susceptibility mapping (QSM). METHODS: In this work, we i) acquire, co-register and transform TCS and QSM imaging from a cohort of 23 PD patients and 27 healthy control subjects into a normalized atlas template space and ii) analyze and compare the 3D spatial distributions of iron accumulation in the midbrain, as detected by a signal increase (TCS+ and QSM+) in both modalities. RESULTS: We achieved sufficiently accurate intra-modal target registration errors (TRE<1 mm) for all MRI volumes and multi-modal TCS-MRI co-localization (TRE<4 mm) for 66.7% of TCS scans. In the caudal part of the midbrain, enlarged TCS+ and QSM+ areas were located within the SN pars compacta in PD patients in comparison to healthy controls. More cranially, overlapping TCS+ and QSM+ areas in PD subjects were found in the area of the ventral tegmental area (VTA). CONCLUSION: Our findings are concordant with several QSM-based studies on iron-related alterations in the area SN pars compacta. They substantiate that TCS+ is an indicator of iron accumulation in Parkinson's disease within and in the vicinity of the SN. Furthermore, they are in favor of an involvement of the VTA and thereby the mesolimbic system in Parkinson's disease.

Altered relaxation times in MRI indicate bronchopulmonary dysplasia.

We developed a MRI protocol using transverse (T2) and longitudinal (T1) mapping sequences to characterise lung structural changes in preterm infants with bronchopulmonary dysplasia (BPD). We prospectively enrolled 61 infants to perform 3-Tesla MRI of the lung in quiet sleep. Statistical analysis was performed using logistic Group Lasso regression and logistic regression. Increased lung T2 relaxation time and decreased lung T1 relaxation time indicated BPD yielding an area under the curve (AUC) of 0.80. Results were confirmed in an independent study cohort (AUC 0.75) and mirrored by lung function testing, indicating the high potential for MRI in future BPD diagnostics. TRIAL REGISTRATION: DRKS00004600.

Bayesian pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging: validation and application.

Tracer-kinetic analysis of dynamic contrast-enhanced magnetic resonance imaging data is commonly performed with the well-known Tofts model and nonlinear least squares (NLLS) regression. This approach yields point estimates of model parameters, uncertainty of these estimates can be assessed e.g. by an additional bootstrapping analysis. Here, we present a Bayesian probabilistic modeling approach for tracer-kinetic analysis with a Tofts model, which yields posterior probability distributions of perfusion parameters and therefore promises a robust and information-enriched alternative based on a framework of probability distributions. In this manuscript, we use the quantitative imaging biomarkers alliance (QIBA) Tofts phantom to evaluate the Bayesian tofts model (BTM) against a bootstrapped NLLS approach. Furthermore, we demonstrate how Bayesian posterior probability distributions can be employed to assess treatment response in a breast cancer DCE-MRI dataset using Cohen's d. Accuracy and precision of the BTM posterior distributions were validated and found to be in good agreement with the NLLS approaches, and assessment of therapy response with respect to uncertainty in parameter estimates was found to be excellent. In conclusion, the Bayesian modeling approach provides an elegant means to determine uncertainty via posterior distributions within a single step and provides honest information about changes in parameter estimates.

Gel dosimetry for three dimensional proton range measurements in anthropomorphic geometries.

Proton beams used for radiotherapy have potential for superior sparing of normal tissue, although range uncertainties are among the main limiting factors in the accuracy of dose delivery. The aim of this study was to benchmark an N-vinylpyrrolidone based polymer gel to perform three-dimensional measurement of geometric proton beam characteristics and especially to test its suitability as a range probe in combination with an anthropomorphic phantom. For single proton pencil beams as well as for 3×3cm2 mono-energy layers depth dose profiles, lateral dose distribution at different depths and proton range were evaluated in simple cubic gel phantoms at different energies from 75 to 115MeV and different dose levels. In addition, a 90MeV mono-energetic beam was delivered to an anthropomorphic 3D printed head phantom, which was filled with gel. Subsequently, all phantoms underwent magnetic resonance imaging using an axial pixel size of 0.68-0.98mm and with slice thicknesses of 2 or 3mm to derive a 3-dimensional distribution of the T2 relaxation time, which correlates with radiation dose. Indices describing lateral dose distribution and proton range were compared against predictions from a treatment planning system (TPS, for cubic and head phantoms) and Monte Carlo simulations (MC, for the head phantom) after manual rigid co-registration with the T2 relaxation time datasets. For all pencil beams, the FWHM agreement with TPS was better than 1mm or 7%. For the mono-energetic layer, the agreement with TPS in this respect was even better than 0.3mm in each case. With respect to range, results from gel measurements differed no more than 0.9mm (1.6%) from values predicted by TPS. In case of the anthropomorphic phantom, deviations with respect to a nominal range of about 61mm as well as in FWHM were slightly higher, namely within 1.0mm and 1.1mm respectively. Average deviations between gel and TPS/MC were similar (-0.3mm±0.4mm/-0.2±0.5mm). In conclusion, polymer gel dosimetry was found to be a valuable tool to determine geometric proton beam properties three-dimensionally and with high spatial resolution in simple cubic as well as in a more complex anthropomorphic phantom. Post registration range errors of the order of 1mm could be achieved. The additional registration uncertainty (95%) was 1mm.

Improved detection of a tumorous involvement of the mesorectal fascia and locoregional lymph nodes in locally advanced rectal cancer using DCE-MRI.

PURPOSE: The prediction of an infiltration of the mesorectal fascia (MRF) and malignant lymph nodes is essential for treatment planning and prognosis of patients with rectal cancer. The aim of this study was to assess the additional diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the detection of a malignant involvement of the MRF and of mesorectal lymph nodes in patients with locally advanced rectal cancer. METHODS: In this prospective study, 22 patients with locally advanced rectal cancer were examined with 1.5-T MRI between September 2012 and April 2015. Histopathological assessment of tumor size, tumor infiltration to the MRF, and malignant involvement of locoregional lymph nodes served as standard of reference. Sensitivity and specificity of detecting MRF infiltration and malignant nodes (nodal cut-off size [NCO] ≥ 5 and ≥ 10 mm, respectively) was determined by conventional MRI (cMRI; precontrast and postcontrast T1-weighted, T2-weighted, and diffusion-weighted images) and by additional semi-quantitative DCE-MRI maps (cMRI+DCE-MRI). RESULTS: Compared to cMRI, additional semi-quantitative DCE-MRI maps significantly increased sensitivity (86 vs. 71% [NCO ≥ 5 mm]/29% [NCO ≥ 10 mm]) and specificity (90 vs. 70% [NCO ≥ 5 mm]) of detecting malignant lymph nodes (p < 0.05). Moreover, DCE-MRI significantly augmented specificity (91 vs. 82%) of discovering a MRF infiltration (p < 0.05), while there was no change in sensitivity (83%; p > 0.05). CONCLUSION: DCE-MRI considerably increases both sensitivity and specificity for the detection of small mesorectal lymph node metastases (≥ 5 mm but < 10 mm) and sufficiently improves specificity of a suspected MRF infiltration in patients with locally advanced rectal cancer.

Detection of single-phase CTA occult vessel occlusions in acute ischemic stroke using CT perfusion-based wavelet-transformed angiography.

OBJECTIVES: To determine the detection rate of intracranial vessel occlusions using CT perfusion-based wavelet-transformed angiography (waveletCTA) in acute ischemic stroke patients, in whom single-phase CTA (spCTA) failed to detect an occlusion. METHODS: Subjects were selected from a cohort of 791 consecutive patients who underwent multiparametric CT including whole-brain CT perfusion. Inclusion criteria were (1) significant cerebral blood flow (CBF) deficit, (2) no evidence of vessel occlusion on spCTA and (3) follow-up-confirmed acute ischemic infarction. waveletCTA was independently analysed by two readers regarding presence and location of vessel occlusions. Logistic regression analysis was performed to identify predictors of waveletCTA-detected occlusions. RESULTS: Fifty-nine patients fulfilled the inclusion criteria. Overall, an occlusion was identified using waveletCTA in 31 (52.5 %) patients with negative spCTA. Out of 47 patients with middle cerebral artery infarction, 27 occlusions (57.4 %) were detected by waveletCTA, mainly located in the M2 (15) and M3 segments (8). The presence of waveletCTA-detected occlusions was associated with larger CBF deficit volumes (odds ratio (OR) = 1.335, p = 0.010) and shorter times from symptom onset (OR = 0.306, p = 0.041). CONCLUSIONS: waveletCTA is able to detect spCTA occult vessel occlusions in about half of acute ischemic stroke patients and may potentially identify more patients eligible for endovascular therapy. KEY POINTS: • waveletCTA is able to detect spCTA occult vessel occlusions in stroke patients. • waveletCTA-detected occlusions are associated with larger cerebral blood flow deficits. • waveletCTA has the potential to identify more patients eligible for endovascular therapy. • waveletCTA implies neither additional radiation exposure nor extra contrast agent.