Follow-up MRIs Research Articles

A deep learning-based comparative MRI model to detect inflammatory changes in rheumatoid arthritis

Rheumatoid Arthritis (RA) is an autoimmune disease that mainly affects joints in the wrist and hands. It typically results in inflamed and painful joints. MRI is one of the most common imaging modalities to detect and monitor possible inflamed RA-related areas, enabling rheumatologists to treat patients more timely and efficiently. Despite the importance of finding and tracking inflamed areas associated with RA in MRI, there is no previously published work on finding pixel-by-pixel changes related to RA between baseline and follow-up MRIs. Therefore, this paper proposes a hypothesis-free deep learning-based model to discover changes in wrist MRIs on a pixel level to detect changes in inflamed areas related to RA without using prior anatomical information. To do this, a combination of a U-Net-based network and image thresholding was utilised to find pixel-level non-trivial changes between baseline and follow-up MRI images. A wrist MRI dataset including 99 individual pairs of MRI images (each pair constructed of baseline and follow-up images) was used to evaluate the proposed model. Data were collected from patients with clinically suspected arthralgia (CSA), defined as patients at risk of developing RA according to their rheumatologist and already had subclinical inflammation on MRI but could not be diagnosed with RA (yet) since they had not developed clinically detectable arthritis. The obtained results were evaluated using an observer study. The evaluation showed that our proposed model is a promising first step toward developing an automatic model to find RA-related inflammatory changes.

MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma

BackgroundIn pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT).Materials and methodsTen randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position.ResultsThe median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from − 3.5 to 5.8 Gy for the pancreatic tail and − 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation.ConclusionInter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.

A Potential Cause for Unexplained Radiation Toxicity in Proton Therapy

Rare but devastating neurological tissue injury by proton therapy is poorly understood. One consideration is that the transition from passively scattered to pencil beam scanning (PBS) proton radiotherapy over the past decade has affected dose rate. We analyzed clinical data acquired at two institutions on a correlation of voxel-wise dose rates and injury of brain tissue (institution 1) and the optic apparatus (institution 2). All radiation-induced toxicities were delineated (Brain/optic apparatus) on follow-up MRIs. A method to calculate dose rates for PBS plans has been implemented at two institutions independently. Institution 1 reports beam-by-beam time-averaged maximum dose rates per voxel (VMDR) using a 100 ms time interval. Data from four patients who incurred brain tissue injury was included. Dose rate volume histograms were prepared for the target, a 1 cm outer ring to the target, and the necrotic region itself. Prescription doses ranged from 30.6 to 60 Gy delivering either 1.8 or 2.0 Gy per fraction. Tissue injury was generally observed in the dose fall-off at the edge of the target. Additionally, we performed LET weighted dose calculation, robustness analysis, and Monte Carlo calculations. Institution 2 presents voxel-wise dose delivered above a selected dose rate threshold, considering values between 30 and 180 Gy/min. The analysis was performed for 2 cases with optical apparatus injuries and one matching non-toxicity case. Both injuries were observed in the chiasma. Patients received 50.4, 50.4 and 55.8 Gy (non-toxicity) in 1.8 Gy fractions. D1 for chiasma was 51.1, 47.2 and 54 Gy, respectively. Mean and (max) LET in chiasma were 4.02 (4.72), 2.49 (3.16) and 3.44 (4.56) keV/µm accordingly. Institution 1 finds distinct dose rate hot spots in the contoured injured brain regions. Mean VMDR values across all beams are lower in targets than in the 1 cm outer ring (80 Gy/min and 82.8 Gy/min, respectively) and elevated to 113 Gy/min for necrotic regions. Neither of the additional computations showed significant increase of dose in the affected areas. Institution 2 observes that chiasmas, which developed radiation injuries, were exposed to higher dose levels delivered at elevated dose rates (> 72 Gy/min) than the chiasma that did not show any radiation injury. D95 above 72 Gy/min for the two volumes identified as radiation injury was 0.25 and 0.12 Gy/fx, while D98 to chiasmas minus radiation injury or chiasma without any injury for the matching case was 0.06, 0.03 and 0 Gy/fx respectively. Using unique formulations to assess voxel-wise dose rates to brain and optic chiasm, two independent institutions observed that regions with elevated dose rates correlated with radiographic radiation injury. An extended retrospective study including a larger patient cohort with radiation-induced toxicity and asymptomatic patients is under way to confirm or refute the presented observations.

Predicting Neurocognitive Decline in Multiple Brain Metastases Patients Undergoing Distributed Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) is the standard of care for treating a limited number (<3) of brain metastasis (BMs), which offers reduced neurotoxicity compared to whole brain radiotherapy (WBRT). Contemporary advancements in SRS made it possible to also commonly treat multiple (>4) BMs (mBMs). Emphasizing the value of preserving quality of life (QoL) after SRS, there is an urgent need for a systematic study of potential neurocognitive decline in patients receiving SRS treatment for mBMs. The purpose of this study is to use routine MRIs to predict neurocognitive decline for patients treated with distributed SRS, allowing for timely and effective treatment strategy design. This study uses data from an institutional phase I/II clinical trial to determine the neurocognitive decline in patients with (>6) mBMs treated with distributed SRS. In the first 12 months post-SRS, participants are followed and evaluated with routine MRIs and the Hopkins Verbal Learning Test-Revised (HVLT-R) at 2 to 3-month intervals. Changes in HVLT-Delayed Recall scores between two visits are used to define neurocognitive decline. For each visit, an in-house deep learning model segments 66 cortical and 55 subcortical brain regions of interest (ROIs) from the T1 structural MRI and extracts 253 ROI features, including the surface area and thickness of cortical ROIs, and the volume of all ROIS. The difference in ROI features between two visits, together with other clinical factors (e.g., prescription, number of BMs, etc.), is considered as one sample. The study included 22 subjects with 91 visits, resulting in 171 samples with neurocognitive decline labels. The entire sample set is split into 10 folds on patient level for cross validation. In each fold, feature engineering is conducted to remove redundancy and to select the most-important features. The top 20% most frequently selected features are applied with Support Vector Machine to predict the neurocognitive decline label of each sample. As a preliminary result, the proposed method achieves an accuracy of 76%, with an area under the curve (AUC) of 0.75, sensitivity of 0.65 and specificity of 0.83 for predicting neurocognitive decline in mBMs SRS patients using only routine T1 MRIs. The volume of lateral occipital complex, the thickness of inferior parietal lobe and postcentral gyrus, and the surface area of lateral orbitofrontal cortex and pars triangularis are identified as the 5 most important features for this task. Our method shows promising findings for post-SRS neurocognitive decline prediction solely based on routine baseline and follow-up MRIs. In addition, it can identify critical brain ROIs associated with the post-SRS cognitive function. This method has the potential to assist treatment planning strategy to help preserve patients' QoL.

OS06.6.A FLAIR-SIGNAL INTENSITY CHANGE AS A PREDICTOR OF PROGRESSIVE GLIOBLASTOMA IN THE EORTC CENTRIC AND CORE STUDIES

Abstract BACKGROUND In patients with glioblastoma, radiological recurrence of enhancing tissue after chemoradiotherapy can originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. In earlier studies, a change of the FLAIR-signal intensity (SI) predicted PD with 18-84% sensitivity and 71-100% specificity, both with quantitative resection cavity to ventricle SI ratio of 7.3. We assessed the rate of FLAIR-signal intensity change in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated or -unmethylated glioblastoma from the randomised CENTRIC and CORE studies (NCT00689221, NCT00813943). These patients were treated with chemoradiotherapy or chemoradiotherapy with cilengitide, an integrin inhibitor. METHODS Patients from both studies with a gross total resection and ≥3 follow-up MRIs were included. The outcome was determined by the modified RANO criteria of 2017. Two researchers evaluated the FLAIR-SI of the resection cavity. A positive SI change was scored qualitatively in case of a visually brighter signal intensity than on the previous MRI. Quantitative analysis was based on a ratio of SI in the resection cavity compared to SI of the ventricles. RESULTS Follow-up was available for 307 patients. Median time from RT to (preliminary) progressive disease was 6.2 months for MGMT promoter-methylated (interquartile range, (iqr)=2.5-14.7) and 6.0 for MGMT promoter-unmethylated glioblastoma (iqr=2.7-8.9). Of the 307 patients, 142 patients showed stable disease, response, or treatment-associated changes and 165 (preliminary) PD at the end of follow-up. A qualitative FLAIR-SI change was found in 61 patients (19.9%) and 44 of these developed (preliminary) PD, with a positive predictive value of 72.1% (95%-CI 59.2-82.9%); positive predictive value was 88.9% for MGMT promoter-unmethylated and 67.4% for MGMT promoter-methylated glioblastoma. We found an overall sensitivity of the FLAIR-SI-change for PD of 26.7% (95%-CI 20.1-34.1%), with ranges of 22.9 to 39.2% depending on MGMT promoter methylation status and treatment allocation; specificity ranged from 88 to 91.3%, with an overall specificity of 88.0% (95%-CI 81.5-92.9%). Median time from first FLAIR-SI to progression was 0 months (iqr=0-2.7) with a range of 0 to 13, and from the brightest signal was 0 months (iqr=0-1.0). The average signal intensity ratio was 10.2 at the time of the brightest signal; further quantitative analyses will be presented. CONCLUSION We confirmed the positive predictive value of a change in FLAIR-signal intensity of the resection cavity for concurrent or subsequent progressive disease in resected glioblastoma. Patients with such a change of the signal intensity should be worked up further on (e.g. PET imaging, biopsy, any clinical change) or else undergo another MRI closely.

Incompleteness of the Circle of Willis and progression of white matter hyperintensities of presumed vascular origin. A longitudinal prospective study in community-dwelling older adults

BackgroundEvidence on the association between anatomical variants of the circle of Willis (CoW) and severity of white matter hyperintensities (WMH) of presumed vascular origin is inconclusive, and no study has evaluated the role of incompleteness of CoW on WMH progression in the follow-up. This study aims to assess the impact of incomplete configurations of the CoW on WMH progression in community-dwelling older adults. MethodsFollowing a prospective longitudinal study design, individuals aged ≥60 years enrolled in the Atahualpa Project Cohort from 2012 to 2019 were invited to receive baseline brain MRI and MRA of intracranial vessels, and those who also had brain MRIs at the end of the study (May 2021) were included in the analysis. Poisson regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess the incidence rate ratio (IRR) of WMH progression according to incompleteness of CoW. ResultsThis study included 254 individuals (mean age: 65.4±5.9 years; 55% women). An incomplete CoW was detected in 99 (39%) subjects. Follow-up MRIs showed WMH progression in 103 (41%) individuals after a median follow-up of 6.5±1.4 years. WMH progression was observed in 58/155 subjects with complete and in 45/99 with incomplete CoW (37% versus 45%; p=0.203). There was no association between incomplete CoW and WMH progression in a multivariate Poisson regression model (IRR: 1.21; 95% C.I.: 0.81 – 1.82). ConclusionsStudy results show that incompleteness of CoW is not involved in WMH progression.

Improving our understanding of the paradoxical protective effect of obesity on radiographic damage: a large magnetic resonance imaging-study in early arthritis.

Obesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression. We studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models). In RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P < 0.001). High BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions.

Arthroscopic decompression of calcific tendinitis without cuff repair.

The aim of this study was to investigate the outcomes of arthroscopic decompression of calcific tendinitis performed without repairing the rotator cuff defect. A total of 99 patients who underwent treatment between December 2013 and August 2019 were retrospectively reviewed. Visual analogue scale (VAS) and American Shoulder and Elbow Surgeons (ASES) scores were reviewed pre- and postoperatively according to the location, size, physical characteristics, and radiological features of the calcific deposits. Additionally, the influence of any residual calcific deposits shown on postoperative radiographs was explored. The healing rate of the unrepaired cuff defect was determined by reviewing the 29 patients who had follow-up MRIs. Statistically significant improvement from pre- to postoperation was seen in all VAS and ASES scores for each group, but no statistical differences were seen between the postoperative scores according to the differences in the features of the calcific deposits. When residual calcification was observed postoperatively, the mean ASES and VAS (rest) scores improved significantly to 95.0 (SD 5.6) and 0.0 (SD 0.0), respectively (p = 0.006 and p < 0.001), and did not differ from those who had the complete removal. Of 29 patients who had follow-up MRIs, six (20.7%) showed signs of an interstitial tear. This group's mean postoperative ASES and VAS (rest) scores improved to excellent levels of 96.0 (SD 3.7) and 0.0 (SD 0.0), respectively, and were similar to those of the 23 patients with normal MRI appearances. Arthroscopic removal of calcific deposits without repairing the rotator cuff defect resulted in significant improvement in function and pain level, regardless of the deposit's location, size, type, and whether or not complete excision was achieved. Despite leaving the defects unrepaired, in the limited number of patients with follow-up MRIs, 23 of 29 patients (79.3%) showed good healing, and the rest, who had persistent signs of interstitial defects on the MRIs, still had excellent outcomes. The removal of calcific deposits without repairing the cuff defects provided excellent outcomes.

Neurocognitive and radiological follow-up of children under 5 years of age treated for medulloblastoma according to the HIT-SKK protocol.

The HIT-SKK protocol is used for low/standard-risk medulloblastomas in young children with the aim to eliminate cranial irradiation and its neuropsychological (NP) sequelae. This therapy includes IV and intraventricular (ITV) methotrexate (MTX) potentially responsible for leukoencephalopathy (LE) and neurocognitive disorders. This study describes the risk factors and course of LE, and investigates its correlation with neurocognitive impact. A retrospective, multicenter study was conducted in 35 children under 5 years old, with a median follow-up of 72 months (range 14 to 130). The main analysis was performed in 30 patients who received cumulative doses of MTX as per-protocol (group 1). Five patients who received higher cumulative doses of MTX were analyzed separately. All follow-up MRIs and NP assessments were centrally reviewed by experts. Twenty patients in group 1 developed LE, grade 2 and 3 abnormalities did not correlate with higher cumulative doses of ITV-MTX (p = 0.698). Considering the most recent NP evaluation, the Full-Scale IQ (FSIQ) and Wechsler indices were in the average to lower average range. The FSIQ was deficient in 6/17 evaluable patients. Cumulative dose of ITV-MTX was almost associated with decreased processing speed competence (p = 0.055) which was the most frequently impaired neurocognitive domain. Neuropsychological assessment scores were not statistically lower in patients with persistent grade 2 LE at the end of follow-up. This study described that the use of cumulative dose of MTX (IV and ITV) according to the HIT-SKK protocol resulted in LE that tented to decrease over time, without significant correlation with a decline in neuro-intellectual skills.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial—a study protocol

BackgroundPartial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients.MethodsThe ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy.DiscussionThis trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients.Trial registrationThe trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Time for change? Radiologists highly concordant assessing change in stenoses on follow-up cervical spine MRI.

There is considerable variability among radiologists when grading spinal canal and foraminal stenosis on MRI. However, to date, studies have not evaluated radiologists' agreement when assessing interval change in cervical spine stenoses. The purpose of this study was to evaluate radiologists' concordance for change in cervical spine stenoses on follow-up MRIs, a major indication for these exams. Initial and follow-up cervical MRIs were retrospectively reviewed by three blinded radiologists. Spinal canal and foramina from C1 through T1 were rated for interval change and concordance between the blinded raters was calculated. The original MRI reports were also reviewed for specific language assessing interval change on the follow-up exams. 40 cervical MRI exams and 40 corresponding MRI follow-ups were assessed. Agreement for interval change in spinal canal and foraminal stenosis was near perfect amongst all readers (kappa values of 0.78-0.94). 97% of the original MRI reports used the standard severity scale. 68% of follow-up MRI reports specifically assessed for change. Blinded radiologists had high agreement when assessing for change in spinal canal and foraminal stenosis on follow-up cervical spine MRIs. Because of inter-rater variability in stenosis grading, reports that do not emphasize change assessment, may imply change that is not truly present. For clarity and consistency in reporting of cervical spine stenoses, change assessment should be emphasized and added to structured reporting templates.

The patients’ experience of neuroimaging of primary brain tumors: a cross-sectional survey study

PurposeTo gain insight into how patients with primary brain tumors experience MRI, follow-up protocols, and gadolinium-based contrast agent (GBCA) use.MethodsPrimary brain tumor patients answered a survey after their MRI exam. Questions were analyzed to determine trends in patients’ experience regarding the scan itself, follow-up frequency, and the use of GBCAs. Subgroup analysis was performed on sex, lesion grade, age, and the number of scans. Subgroup comparison was made using the Pearson chi-square test and the Mann–Whitney U-test for categorical and ordinal questions, respectively.ResultsOf the 100 patients, 93 had a histopathologically confirmed diagnosis, and seven were considered to have a slow-growing low-grade tumor after multidisciplinary assessment and follow-up. 61/100 patients were male, with a mean age ± standard deviation of 44 ± 14 years and 46 ± 13 years for the females. Fifty-nine patients had low-grade tumors. Patients consistently underestimated the number of their previous scans. 92% of primary brain tumor patients did not experience the MRI as bothering and 78% would not change the number of follow-up MRIs. 63% of the patients would prefer GBCA-free MRI scans if diagnostically equally accurate. Women found the MRI and receiving intravenous cannulas significantly more uncomfortable than men (p = 0.003). Age, diagnosis, and the number of previous scans had no relevant impact on the patient experience.ConclusionPatients with primary brain tumors experienced current neuro-oncological MRI practice as positive. Especially women would, however, prefer GBCA-free imaging if diagnostically equally accurate. Patient knowledge of GBCAs was limited, indicating improvable patient information.

Correlation between the Clinical Course of CRMO Lesions and the Imaging Characteristics on Follow-up MRIs

Objective: To evaluate the correlation between the clinical course of chronic recurrent multifocal osteomyelitis (CRMO) lesions and their imaging characteristics on follow-up MRIs. Material and Methods: Two musculoskeletal fellowship-trained radiologists retrospectively reviewed the initial and follow-up MRI images of 9 CRMO patients who were treated in our institution from 2008 to 2018. Evaluation of clinical course was based on symptomatology, lab results and physical examination and was compared to MRI findings, on follow-up MRIs. Results: Thirty-five CRMO lesions in 9 patients were identified. Patient’s ages ranged from 4 to 15 years with a mean age of 10 years (S.D.±3.22). Six of the 9 patients were female. Only 21 of 35 lesions had been longitudinally followed by MRI. Of the 39 follow-up MRI exams, there was clinical improvement 15 times, and 24 times there was no clinical improvement confirmed by the clinician. Three MRI features: 1) bone marrow edema (BME) size, 2) BME signal intensity and 3) periosteal edema, significantly correlated with the clinical course (p-value&lt;0.001). When there was the improvement of all these three findings, the correlation with clinical improvement was high with 80% sensitivity and 100% specificity. The area under the receiver operator characteristic curve was 0.90 (95% confidence interval 0.795-1.005). Fourteen silent clinical lesions were also identified. Conclusion: Bone marrow edema and periosteal edema correlated best with the clinical course of CRMO patients on follow-up MRIs.

Role of novel policy implementation for Gamma Knife (GK) procedures in improving access to neurosurgical care in lower middle income countries (LMICs) GK in LMICs

BackgroundThe high cost of GK machines with resultant scarcity of GK centers, coupled to additional cost of contrast MRI brain makes it nearly impossible for the vast majority of the population without health insurance in LMICs to have access to this advancement in management. MethodsAIIMS, Delhi is the premier public funded hospital in India with the largest Neurosurgical department in the country. We implemented a single payment policy which would cover the treatment and all subsequent GK treatments as well as Follow-up MRIs of the patient. The program was named ‘Gamma Knife for life’ and implemented in 2015. To check the efficacy, we conducted a retrospective analysis of the Neurosurgery cases managed before and after the implementation of this scheme in the last 12 years. ResultsPrior to implementation of the ‘Gamma Knife for life’ program, a total of 24,703 patients underwent Neurosurgical procedures in the years 2009–2015. Of these, only 2017 (8.16%) were GK procedures. In the years following the introduction of the program, the total number of neurosurgical procedures was 23,030 with 2947 (12.8%) being the GK procedures This difference in the number of GK procedures before and after the application of ‘Gamma Knife for Life’ was statistically significant (p = 0.026). The highest number of GK procedures (n = 789) reported so far were in 2020–21. ConclusionsEnsuring holistic care by providing for not only the initial GK procedure but all subsequent procedures, as well as follow-up MRI's can improve the quality and consistency of care, especially in LMICs.

Brain segmentation in patients with perinatal arterial ischemic stroke

BackgroundPerinatal arterial ischemic stroke (PAIS) is associated with adverse neurological outcomes. Quantification of ischemic lesions and consequent brain development in newborn infants relies on labor-intensive manual assessment of brain tissues and ischemic lesions. Hence, we propose an automatic method utilizing convolutional neural networks (CNNs) to segment brain tissues and ischemic lesions in MRI scans of infants suffering from PAIS. Materials and MethodsThis single-center retrospective study included 115 patients with PAIS that underwent MRI after the stroke onset (baseline) and after three months (follow-up). Nine baseline and 12 follow-up MRI scans were manually annotated to provide reference segmentations (white matter, gray matter, basal ganglia and thalami, brainstem, ventricles, extra-ventricular cerebrospinal fluid, and cerebellum, and additionally on the baseline scans the ischemic lesions). Two CNNs were trained to perform automatic segmentation on the baseline and follow-up MRIs, respectively. Automatic segmentations were quantitatively evaluated using the Dice coefficient (DC) and the mean surface distance (MSD). Volumetric agreement between segmentations that were manually and automatically obtained was computed. Moreover, the scan quality and automatic segmentations were qualitatively evaluated in a larger set of MRIs without manual annotation by two experts. In addition, the scan quality was qualitatively evaluated in these scans to establish its impact on the automatic segmentation performance. ResultsAutomatic brain tissue segmentation led to a DC and MSD between 0.78–0.92 and 0.18–1.08 mm for baseline, and between 0.88–0.95 and 0.10–0.58 mm for follow-up scans, respectively. For the ischemic lesions at baseline the DC and MSD were between 0.72–0.86 and 1.23–2.18 mm, respectively. Volumetric measurements indicated limited oversegmentation of the extra-ventricular cerebrospinal fluid in both the follow-up and baseline scans, oversegmentation of the ischemic lesions in the left hemisphere, and undersegmentation of the ischemic lesions in the right hemisphere. In scans without imaging artifacts, brain tissue segmentation was graded as excellent in more than 85% and 91% of cases, respectively for the baseline and follow-up scans. For the ischemic lesions at baseline, this was in 61% of cases. ConclusionsAutomatic segmentation of brain tissue and ischemic lesions in MRI scans of patients with PAIS is feasible. The method may allow evaluation of the brain development and efficacy of treatment in large datasets.

Postoperative delirium is associated with grey matter brain volume loss.

Delirium is associated with long-term cognitive dysfunction and with increased brain atrophy. However, it is unclear whether these problems result from or predisposes to delirium. We aimed to investigate preoperative to postoperative brain changes, as well as the role of delirium in these changes over time. We investigated the effects of surgery and postoperative delirium with brain MRIs made before and 3 months after major elective surgery in 299 elderly patients, and an MRI with a 3 months follow-up MRI in 48 non-surgical control participants. To study the effects of surgery and delirium, we compared brain volumes, white matter hyperintensities and brain infarcts between baseline and follow-up MRIs, using multiple regression analyses adjusting for possible confounders. Within the patients group, 37 persons (12%) developed postoperative delirium. Surgical patients showed a greater decrease in grey matter volume than non-surgical control participants [linear regression: B (95% confidence interval) = -0.65% of intracranial volume (-1.01 to -0.29, P < 0.005)]. Within the surgery group, delirium was associated with a greater decrease in grey matter volume [B (95% confidence interval): -0.44% of intracranial volume (-0.82 to -0.06, P = 0.02)]. Furthermore, within the patients, delirium was associated with a non-significantly increased risk of a new postoperative brain infarct [logistic regression: odds ratio (95% confidence interval): 2.8 (0.7-11.1), P = 0.14]. Our study was the first to investigate the association between delirium and preoperative to postoperative brain volume changes, suggesting that delirium is associated with increased progression of grey matter volume loss.

Development of New or Enlarging MRI Lesions Outside of Clinical Attacks in MOG-Antibody-Associated Disease

Objective To determine the frequency of new/enlarging T2 or enhancing asymptomatic lesions in myelin-oligodendrocyte-glycoprotein-antibody-associated-disease (MOGAD) and compare to multiple sclerosis (MS) and aquaporin-4 antibody-positive-neuromyelitis-optica-spectrum-disorder (AQP4+NMOSD). Background Data on new asymptomatic lesions in MOGAD is limited. Design/Methods We retrospectively identified Mayo Clinic MOGAD patients with inclusion criteria of: 1)MOG-IgG positivity by live-cell-based-assay; 2)Fulfilling current MOGAD diagnostic criteria; 3) Baseline and follow-up paired MRIs without interval attacks. Paired MRIs (baseline and follow-up) were categorized as either attack-to-remission or remission-to-remission scans. A neurologist and neuroradiologist reviewed MRIs (T2-FLAIR brain, T2 spine, and T1-post-gadolinium brain and spine) to identify new/enlarging lesions. A subset of MOGAD patients matched for follow-up interval were compared to MS and AQP4+NMOSD patients. Results We included 105 MOGAD patients (median age, 31 years[range, 3-80]; 60% female) with 373 paired MRIs (brain, 213, spine 160). In total, 13/373 (3%) scans (10/105 patients) had one or more new/enlarging T2-lesions (brain, 12/213[5.6%]; spine, 1/160[0.6%]) and 8/367 (2%) had enhancing lesions. New spinal lesions were rare across all groups (0-4%). T2 lesions occurred more commonly in attack-remission scans (8/171[4.7%]) then remission-remission scans (5/202[2.4%]). Clinical characteristics did not differ between patients who developed new/enlarging lesions and those who did not. Maintenance immunosuppressants were used in 44/105 (42%) patients. New/enlarging lesions did not predict future clinical relapse. New brain lesions were less in MOGAD (1/25[4%]) than MS (14/26[54%], p &lt; 0.0001) but did not differ from AQP4+NMOSD (1/13[8%], p = 1.0) in subgroup analysis. Conclusions New brain MRI lesions rarely develop outside of attacks in MOGAD which differs from MS. Surveillance MRI in MOGAD may have limited utility as a surrogate biomarker of disease activity in clinical practice and for clinical trials.

Placement of a polyurethane implant is not associated with a chondroprotective effect: comparative study with cases of isolated medial meniscectomy with at least five years of follow-up.

Our main objective was to evaluate clinically and radiologically and compare patients who had undergone partial meniscectomy alone, with those who had received a partial meniscectomy in which a polyurethane implant was placed, with a minimum follow-up of 5years. We performed a prospective cohort study. Patients were randomly distributed into Group A if they only received meniscectomy or Group B if they received meniscectomy plus a meniscal implant (Actifit®). We performed preoperative, postoperative, and 5-year-follow-up functional and radiological evaluations (magnetic resonance imaging). Twelve patients (40%) were treated with meniscal implants (Group B); 18 (60%) were treated with a conventional meniscectomy (Group A). Tegner, Lysholm and KOOS scores were evaluated prior to surgery and at 5-year follow-up. Only the Lysholm score showed a significant difference between groups, with a score increase between the preoperative evaluation and the 5-year follow-up evaluation (p = 0.013). Preoperative and postoperative MRIs were both available in 19 cases (63.3%). Long-term follow-up MRIs were performed in 11 cases of group B. No significant differences were found in functional outcomes or MRI findings (WORMS cartilage score increase p = 0.360). Although total reabsorptions of the collagen meniscus implant were not statistically significant in younger patients, a tendency towards a higher reabsorption process was seen in older patients (p = 0.015). The placement of a polyurethane implant after a wide meniscectomy is not accompanied by a chondroprotective effect over time. There is no functional difference between implant placement and isolated meniscectomy. There is a discrepancy between good clinical results and radiologic appearance of these implants and their underlying cartilage. II, therapeutic study.

Stereotactic Radiosurgery and Anti-PD-1 + CTLA-4 Therapy, Anti-PD-1 Therapy, Anti-CTLA-4 Therapy, BRAF/MEK Inhibitors, BRAF Inhibitor, or Conventional Chemotherapy for the Management of Melanoma Brain Metastases

<h3>Purpose/Objective(s)</h3> Immunotherapy and targeted BRAF/MEK inhibition have revolutionized the systemic management of advanced melanoma with sustained intracranial responses noted in prospective clinical trials. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK inhibitors(i), BRAF inhibitor, or conventional chemotherapy. <h3>Materials/Methods</h3> Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. The assigned regimen was the last course of systemic treatment to avoid the effects of multiple systemic agents influencing clinical end points. The primary endpoint was distant MBM control with secondary endpoints of local MBM control (defined as a sustained less than >20% volume increase on follow-up MRIs) and OS from SRS. <h3>Results</h3> In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 to 2020 were identified: Median SRS dose was 24 Gy (range: 15-24 Gy) all in a single fraction. Median follow-up using the reverse Kaplan-Meier (KM) method was 41.8 months. No significant differences were noted in age (p=0.10), gender (p=0.47), Karnofsky Performance Scale (KPS) (p=0.27), treated gross tumor volume (p=0.07), number of MBM treated per patient (0.08), or Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) (p=0.28) between groups. Twelve-month KM OS rates by DS-GPA were 17%, 33%, 54%, and 69% for scores 0-1, 1.5-2, 2.5-3, 3.5-4, respectively (p=<0.001). Twelve-month KM distant MBM control rates were 42%, 63%, 24%, 44%, 23%, and 16% (p=<0.001) for SRS with anti-PD-1 + CTLA-4, anti-PD-1, anti-CTLA-4, BRAF/MEK inhibitors (i), BRAF-i, or chemotherapy, respectively. The 12-month KM local MBM control rates were 86%, 77%, 79%, 85%, 87%, and 57% (p=<0.001). Twelve-month OS rates from SRS diagnosis were 68%, 59%, 45%, 62%, 21%, and 15% (p=<0.001). On multivariate analysis (MVA), 2-5 MBM (HR 1.72, 95% CI: 1.1-42.7, p=0.02) and >5 MBM being treated (HR 2.65, 95% CI: 1.65-4.25, p=<0.001) was associated with worse distant MBM control. Treatment with anti-PD-1 therapy (HR 0.24, 95% CI:0.14-0.41, p=0.0009) was associated with improved distant MBM control. MVA also showed, treatment with anti-PD-1 (HR 0.27, 95% CI: 0.17-0.41, P=0.0007) and anti-PD-1 + CTLA-4 (HR 0.29, 95% CI: 0.15-0.53, p=0.01) were both associated with increased OS. The rates of symptomatic radiation necrosis were 2%, 2%, 1%, 1%, 2%, and 3% (p=0.93). <h3>Conclusion</h3> To our knowledge, this is the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in distant MBM control as well as OS by systemic therapy.

Neuromuscular Toxicity and Dose-Volume Relationships Following SBRT for Bone Oligometastases: Post-Hoc Analysis of Two Ongoing Clinical Trials

<h3>Purpose/Objective(s)</h3> Growing evidence suggests that stereotactic body radiotherapy (SBRT) is effective for oligometastatic disease. Currently, there is limited data to define dose-volume relationships between muscle and adipose tissues and neuromuscular toxicities. In this post hoc analysis, we evaluated these associations in patients enrolled in two phase II clinical trials (NCT03575611, NCT03599765) where bone oligometastases were ablated with SBRT. <h3>Materials/Methods</h3> We reviewed three-fraction SBRT treatment plans for bone oligometastases where total dose ranged from 24-36 Gy. We contoured muscle and adjacent soft tissue receiving at least 10Gy based on anatomical function (e.g., hip flexors) and defined the largest-volume group as the most-affected functional muscle group (MFMG). Muscle and adipose tissues within MFMGs (MFMG-m and MFMG-a respectively) were further delineated by semi-automated contouring scripts using previously validated CT Hounsfield unit ranges for muscle (-29 to +150 HU) and adipose (-190 to -30 HU). Associations between neuromuscular adverse events (AE) (graded by Common Terminology Criteria for Adverse Events version 5) with dose to 2cc-30cc of contoured volumes (D2cc-D30cc) and clinical variables (BMI, ECOG, etc.) were assessed using two-sided Mann-Whitney U tests. Results were considered significant at P<0.0071 with Bonferroni correction. <h3>Results</h3> We evaluated 43 treatment plans for 37 patients with target lesions in the pelvic girdle (n=18), rib (n=15), femur (n=4), lumbar vertebra (n=2), scapula (n=2), and sternum (n=2). Three patients (8.1%) experienced grade 3 hip pain, 1 patient (2.7%) had grade 2 hip pain, and 2 patients (5.4%) had grade 1 hip or rib pain. There were no grade 4 or 5 AEs. Median time to AE was 2.3 months (range: 1.2–4.5 months). Patients with AEs had significantly higher MFMG D25cc (median = 28.4 vs 18.6Gy; p=0.004), MFMG-m D25cc (median = 27.7 vs 17.3Gy; p=0.006), and MFMG-a D5cc (median = 30.2 vs 18.9Gy; p=0.006) compared to pain-free patients. We identified a dose/volume threshold at MFMG D25cc > 25 Gy, where 5/11 (45.5%) treatment plans above and 1/32 (3.1%) below this threshold led to AEs, corresponding to an odds ratio of 25.8. There was no relationship between AEs and BMI, ECOG score, or demographics. No local tumor recurrences occurred with median follow-up of 15.5 months (range: 3.1–35.4 months). Two patients with grade 3 AEs after SBRT to pelvic girdle lesions had 3- and 5-month follow-up MRIs which identified soft tissue edema consistent with our findings. <h3>Conclusion</h3> Preliminary results from two prospective trials suggests that SBRT for bone oligometastases can be conducted safely with excellent tumor control and minimal toxicity. We propose that MFMG D25cc be limited to 25 Gy to avoid symptomatic neuromuscular toxicity. Future studies are needed for dose criteria verification.