Real-time myocardial landmark tracking for MRI-guided cardiac radio-ablation using Gaussian Processes

The high speed of cardiorespiratory motion introduces a unique challenge for cardiac stereotactic radio-ablation (STAR) treatments with the MR-linac. Such treatments require tracking myocardial landmarks with a maximum latency of 100 ms, which includes the acquisition of the required data. The aim of this study is to present a new method that allows to track myocardial landmarks from few readouts of MRI data, thereby achieving a latency sufficient for STAR treatments. We present a tracking framework that requires only few readouts of k-space data as input, which can be acquired at least an order of magnitude faster than MR-images. Combined with the real-time tracking speed of a probabilistic machine learning framework called Gaussian Processes, this allows to track myocardial landmarks with a sufficiently low latency for cardiac STAR guidance, including both the acquisition of required data, and the tracking inference. The framework is demonstrated in 2D on a motion phantom, and in vivo on volunteers and a ventricular tachycardia (arrhythmia) patient. Moreover, the feasibility of an extension to 3D was demonstrated by in silico 3D experiments with a digital motion phantom. The framework was compared with template matching - a reference, image-based, method - and linear regression methods. Results indicate an order of magnitude lower total latency (<10 ms) for the proposed framework in comparison with alternative methods. The root-mean-square-distances and mean end-point-distance with the reference tracking method was less than 0.8 mm for all experiments, showing excellent (sub-voxel) agreement. The high accuracy in combination with a total latency of less than 10 ms - including data acquisition and processing - make the proposed method a suitable candidate for tracking during STAR treatments

Influenza season influence on outcome of new nodules in the NELSON study

We evaluated the impact of the influenza season on outcome of new lung nodules in a LDCT lung cancer screening trial population. NELSON-trial participants with ≥ 1 new nodule detected in screening rounds two and three were included. Outcome (resolution or persistence) of new nodules detected per season was calculated and compared. Winter (influenza season) was defined as 1st October to 31st March, and compared to the summer (hay-fever season), 1st April to 30th September. Overall, 820 new nodules were reported in 529 participants. Of the total new nodules, 482 (59%) were reported during winter. When considering the outcome of all new nodules, there was no statistically significant association between summer and resolving nodules (OR 1.07 [CI 1.00-1.15], p = 0.066), also when looking at the largest nodule per participant (OR 1.37 [CI 0.95-1.98], p = 0.094). Similarly, there was no statistically significant association between season and screen detected cancers (OR 0.47 [CI 0.18-1.23], p = 0.123). To conclude, in this lung cancer screening population, there was no statistically significant association between influenza season and outcome of new lung nodules. Hence, we recommend new nodule management strategy is not influenced by the season in which the nodule is detected.</p

Diffuse idiopathic skeletal hyperostosis of the cervical spine causing dysphagia and airway obstruction: an updated systematic review

BACKGROUND AND CONTEXT: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by growing ossifications of spinal entheses and tendons, which may cause trachea and esophagus compression when located anteriorly in the cervical spine. PURPOSE: Our previous systematic review on the epidemiological and clinical knowledge of dysphagia and airway obstruction caused by cervical DISH was updated, with a focus on (surgical) treatment and outcomes. STUDY DESIGN: A systematic review of the literature was performed. METHODS: Publications in Medline and EMBASE from July 2010 to June 2021 were searched. Two investigators performed data extraction and study specific quality assessment. RESULTS: A total of 138 articles (112 case reports and 26 case series) were included, describing 419 patients with dysphagia and/or airway obstruction. The mean age of the patient group was 67.3 years (range: 35–91 years), and 85.4% was male. An evident increase of published cases was observed within the last decade. Surgical treatment was chosen for 66% of patients with the anterolateral approach most commonly used. The total complication rate after surgery was 22.1%, with 12.7% occurring within 1 month after intervention. Improvement of dysphagia was observed in 95.5% of operated patients. After a mean follow-up of 3.7 years (range: 0.4–9.0 years), dysphagia recurred in 12 surgically treated patients (4%), of which five patients had osteophyte regrowth. CONCLUSIONS: The number of published cases of dysphagia in patients with DISH has doubled in the last decade compared to our previous review. Yet, randomized studies or guidelines on the treatment or prevention on recurrence are lacking. Surgical treatment is effective and has low (major) complication rates. Common trends established across the cases in our study may help improve our understanding and management of dysphagia and airway obstruction in cervical DISH

Influenza season influence on outcome of new nodules in the NELSON study

We evaluated the impact of the influenza season on outcome of new lung nodules in a LDCT lung cancer screening trial population. NELSON-trial participants with ≥ 1 new nodule detected in screening rounds two and three were included. Outcome (resolution or persistence) of new nodules detected per season was calculated and compared. Winter (influenza season) was defined as 1st October to 31st March, and compared to the summer (hay-fever season), 1st April to 30th September. Overall, 820 new nodules were reported in 529 participants. Of the total new nodules, 482 (59%) were reported during winter. When considering the outcome of all new nodules, there was no statistically significant association between summer and resolving nodules (OR 1.07 [CI 1.00-1.15], p = 0.066), also when looking at the largest nodule per participant (OR 1.37 [CI 0.95-1.98], p = 0.094). Similarly, there was no statistically significant association between season and screen detected cancers (OR 0.47 [CI 0.18-1.23], p = 0.123). To conclude, in this lung cancer screening population, there was no statistically significant association between influenza season and outcome of new lung nodules. Hence, we recommend new nodule management strategy is not influenced by the season in which the nodule is detected

On the feasibility of cardiac substructure sparing in magnetic resonance imaging guided stereotactic lung radiotherapy

Background: Lung stereotactic body radiotherapy (SBRT) has proven an effective treatment for medically inoperable lung tumors, even for (ultra-)central tumors. Recently, there has been growing interest in radiation-induced cardiac toxicity in lung radiotherapy. More specifically, dose to cardiac (sub-)structures (CS) was found to correlate with survival after radiotherapy. Purpose: Our goal is first, to investigate the percentage of patients who require CS sparing in an magnetic resonance imaging guided lung SBRT workflow, and second, to quantify how successful implementation of cardiac sparing would be. Methods: The patient cohort consists of 34 patients with stage II–IV lung cancer who were treated with SBRT between 2017 and 2020. A mid-position computed tomography (CT) image was used to create treatment plans for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) following clinical templates. Under guidance of a cardio-thoracic radiologist, 11 CS were contoured manually for each patient. Dose constraints for five CS were extracted from the literature. Patients were stratified according to their need for cardiac sparing depending on the CS dose in their non-CS constrained MR-linac treatment plans. Cardiac sparing treatment plans (CSPs) were then created and dosimetrically compared with their non-CS constrained treatment plan counterparts. CSPs complied with the departmental constraints and were considered successful when fulfilling all CS constraints, and partially successful if some CS constraints could be fulfilled. Predictors for the need for and feasibility of cardiac sparing were explored, specifically planning target volume (PTV) size, cranio-caudal (CC) distance, 3D distance, and in-field overlap volume histograms (iOVH). Results: 47% of the patients (16 out of 34) were in need of cardiac sparing. A successful CSP could be created for 62.5% (10 out of 16) of these patients. Partially successful CSPs still complied with two to four CS constraints. No significant difference in dose to organs at risk (OARs) or targets was identified between CSPs and the corresponding non-CS constrained MR-linac plans. The need for cardiac sparing was found to correlate with distance in the CC direction between target and all of the individual CS (Mann–Whitney U-test p-values <10 −6). iOVHs revealed that complying with dose constraints for CS is primarily determined by in-plane distance and secondarily by PTV size. Conclusion: We demonstrated that CS can be successfully spared in lung SBRT on the MR-linac for most of this patient cohort, without compromising doses to the tumor or to other OARs. CC distance between the target and CS can be used to predict the need for cardiac sparing. iOVHs, in combination with PTV size, can be used to predict if cardiac sparing will be successful for all constrained CS except the left ventricle

Stereotactic body radiotherapy of central lung tumours using a 1.5 T MR-linac: First clinical experiences

BACKGROUND: MRI-guidance may aid better discrimination between Organs at Risk (OARs) and target volumes in proximity of the mediastinum. We report the first clinical experiences with Stereotactic Body Radiotherapy (SBRT) of (ultra)central lung tumours on a 1.5 T MR-linac. MATERIALS AND METHODS: Patients with an (ultra)central lung tumour were selected for MR-linac based SBRT treatment. A T2-weighted 3D sequence MRI acquired during free breathing was used for daily plan adaption. Prior to each fraction, contours of Internal Target Volume (ITV) and OARs were deformably propagated and amended by a radiation oncologist. Inter-fractional changes in volumes and coverage of target volumes as well as doses in OARs were evaluated in offline and online treatment plans. RESULTS: Ten patients were treated and completed 60 Gy in 8 or 12 fractions. In total 104 fractions were delivered. The median time in the treatment room was 41 min with a median beam-on time of 8.9 min. No grade ≥3 acute toxicity was observed. In two patients, the ITV significantly decreased during treatment (58 % and 37 %, respectively) due to tumour shrinkage. In the other patients, 81 % of online ITVs were within ±15 % of the volume of fraction 1. Comparison with the pre-treatment plan showed that ITV coverage of the online plan was similar in 52 % and improved in 34 % of cases. Adaptation to meet OAR constraints, led to decreased ITV coverage in 14 %. CONCLUSIONS: We describe the workflow for MR-guided Radiotherapy and the feasibility of using 1.5 T MR-linac for SBRT of (ultra) central lung tumours

Prospective of 31 P MR Spectroscopy in Hepatopancreatobiliary Cancer: A Systematic Review of the Literature.

BACKGROUND: The incidence of liver and pancreatic cancer is rising. Patients benefit from current treatments, but there are limitations in the evaluation of (early) response to treatment. Tumor metabolic alterations can be measured noninvasively with phosphorus ( 31 P) magnetic resonance spectroscopy (MRS). PURPOSE: To conduct a quantitative analysis of the available literature on 31 P MRS performed in hepatopancreatobiliary cancer and to provide insight into its current and potential for therapy (non-) response assessment. POPULATION: Patients with hepatopancreatobiliary cancer. FIELD STRENGTH/SEQUENCE: 31 P MRS. ASSESSMENT: The PubMed, EMBASE, and Cochrane library databases were systematically searched for studies published to 17 March 17, 2022. All 31 P MRS studies in hepatopancreatobiliary cancer reporting 31 P metabolite levels were included. STATISTICAL TESTS: Relative differences in 31 P metabolite levels/ratios between patients before therapy and healthy controls, and the relative changes in 31 P metabolite levels/ratios in patients before and after therapy were determined. RESULTS: The search yielded 10 studies, comprising 301 subjects, of whom 132 (44%) healthy volunteers and 169 (56%) patients with liver cancer of various etiology. To date, 31 P MRS has not been applied in pancreatic cancer. In liver cancer, alterations in levels of 31 P metabolites involved in cell proliferation (phosphomonoesters [PMEs] and phosphodiesters [PDEs]) and energy metabolism (ATP and inorganic phosphate [Pi]) were observed. In particular, liver tumors were associated with elevations of PME/PDE and PME/Pi compared to healthy liver tissue, although there was a broad variety among studies (elevations of 2%-267% and 21%-233%, respectively). Changes in PME/PDE in liver tumors upon therapy were substantial, yet very heterogeneous and both decreases and increases were observed, whereas PME/Pi was consistently decreased after therapy in all studies (-13% to -76%). DATA CONCLUSION: 31 P MRS has great potential for treatment monitoring in oncology. Future studies are needed to correlate the changes in 31 P metabolite levels in hepatopancreatobiliary tumors with treatment response. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2

Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial

BACKGROUND There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3, and year 5.5 or no screening. We obtained data on cancer diagnosis and the date and cause of death through linkages with national registries in the Netherlands and Belgium, and a review committee confirmed lung cancer as the cause of death when possible. A minimum follow-up of 10 years until December 31, 2015, was completed for all participants. RESULTS Among men, the average adherence to CT screening was 90.0%. On average, 9.2% of the screened participants underwent at least one additional CT scan (initially indeterminate). The overall referral rate for suspicious nodules was 2.1%. At 10 years of follow-up, the incidence of lung cancer was 5.58 cases per 1000 personyears in the screening group and 4.91 cases per 1000 person-years in the control group; lung-cancer mortality was 2.50 deaths per 1000 person-years and 3.30 deaths per 1000 person-years, respectively. The cumulative rate ratio for death from lung cancer at 10 years was 0.76 (95% confidence interval [CI], 0.61 to 0.94; P = 0.01) in the screening group as compared with the control group, similar to the values at years 8 and 9. Among women, the rate ratio was 0.67 (95% CI, 0.38 to 1.14) at 10 years of follow-up, with values of 0.41 to 0.52 in years 7 through 9. CONCLUSIONS In this trial involving high-risk persons, lung-cancer mortality was significantly lower among those who underwent volume CT screening than among those who underwent no screening. There were low rates of follow-up procedures for results suggestive of lung cancer. (Funded by the Netherlands Organization of Health Research and Development and others; NELSON Netherlands Trial Register number, NL580.)

Feasibility of cardiac-synchronized quantitative T1 and T2 mapping on a hybrid 1.5 Tesla magnetic resonance imaging and linear accelerator system

Background and Purpose: The heart is important in radiotherapy either as target or organ at risk. Quantitative T1 and T2 cardiac magnetic resonance imaging (qMRI) may aid in target definition for cardiac radioablation, and imaging biomarker for cardiotoxicity assessment. Hybrid MR-linac devices could facilitate daily cardiac qMRI of the heart in radiotherapy. The aim of this work was therefore to enable cardiac-synchronized T1 and T2 mapping on a 1.5 T MR-linac and test the reproducibility of these sequences on phantoms and in vivo between the MR-linac and a diagnostic 1.5 T MRI scanner. Materials and methods: Cardiac-synchronized MRI was performed on the MR-linac using a wireless peripheral pulse-oximeter unit. Diagnostically used T1 and T2 mapping sequences were acquired twice on the MR-linac and on a 1.5 T MR-simulator for a gel phantom and 5 healthy volunteers in breath-hold. Phantom T1 and T2 values were compared to gold-standard measurements and percentage errors (PE) were computed, where negative/positive PE indicate underestimations/overestimations. Manually selected regions-of-interest were used for in vivo intra/inter scanner evaluation. Results: Cardiac-synchronized T1 and T2 qMRI was enabled after successful hardware installation on the MR-linac. From the phantom experiments, the measured T1/T2 relaxation times had a maximum percentage error (PE) of -4.4%/-8.8% on the MR-simulator and a maximum PE of -3.2%/+8.6% on the MR-linac. Mean T1/T2 of the myocardium were 1012 ± 34/51 ± 2 ms on the MR-simulator and 1034 ± 42/51 ± 1 ms on the MR-linac. Conclusions: Accurate cardiac-synchronized T1 and T2 mapping is feasible on a 1.5 T MR-linac and might enable novel plan adaptation workflows and cardiotoxicity assessments

Feasibility of P-31 spectroscopic imaging at 7 T in lung carcinoma patients

Currently, it is difficult to predict effective therapy response to molecular therapies for the treatment of lung cancer based solely on anatomical images. 31 P MR spectroscopic imaging could provide as a non-invasive method to monitor potential biomarkers for early therapy evaluation, a necessity to improve personalized care and reduce cost. However, surface coils limit the imaging volume in conventional 31 P MRSI. High-energetic adiabatic RF pulses are required to achieve flip angle homogeneity but lead to high SAR. Birdcage coils permit use of conventional amplitude modulated pulses, even over large FOV, potentially decreasing overall SAR massively. Here, we investigate the feasibility of 3D 31 P MRSI at 7 T in lung carcinoma patients using an integrated 31 P birdcage body coil in combination with either a dual-coil or a 16-channel receiver. Simulations showed a maximum decrease in SNR per unit of time of 8% for flip angle deviations in short TR low flip-angle excitation 3D CSI. The minimal SNR loss allowed for fast 3D CSI without time-consuming calibration steps (>10:00 min.). 31 P spectra from four lung carcinoma patients were acquired within 29:00 minutes and with high SNR using both receivers. The latter allowed discrimination of individual phosphodiesters, inorganic phosphate, phosphocreatine and ATP. The receiver array allowed for an increased FOV compared to the dual-coil receiver. 3D 31 P-CSI were acquired successfully in four lung carcinoma patients using the integrated 31 P body coil at ultra-high field. The increased spectral resolution at 7 T allowed differentiation of multiple 31 P metabolites related to phospholipid and energy metabolism. Simulations provide motivation to exclude 31 P B1 calibrations, potentially decreasing total scan duration. Employing large receiver arrays improves the field of view allowing for full organ coverage. 31 P MRSI is feasible in lung carcinoma patients and has potential as a non-invasive method for monitoring personalized therapy response in lung tumors