General Algorithm Applicability in Determining DBS Lead Orientation: Adapting 2D and 3D X-Ray Techniques for SenSightTM Leads.

INTRODUCTION: With recent advancements in deep brain stimulation (DBS), directional leads featuring segmented contacts have been introduced, allowing for targeted stimulation of specific brain regions. Given that manufacturers employ diverse markers for lead orientation, our investigation focuses on the adaptability of the 2017 techniques proposed by the Cologne research group for lead orientation determination. METHODS: We tailored the two separate 2D and 3D X-ray-based techniques published in 2017 and originally developed for C-shaped markers, to the dual-marker of the Medtronic SenSight™ lead. In a retrospective patient study, we evaluated their feasibility and consistency by comparing the degree of agreement between the two methods. RESULTS: The Bland-Altman plot showed favorable concordance without any noticeable systematic errors. The mean difference was 0.79°, with limits of agreement spanning from 21.4° to -19.8°. The algorithms demonstrated high reliability, evidenced by an intraclass correlation coefficient of 0.99 (p < 0.001). CONCLUSION: The 2D and 3D algorithms, initially formulated for discerning the circular orientation of a C-shaped marker, were adapted to the marker of the Medtronic SenSight™ lead. Statistical analyses revealed a significant level of agreement between the two methods. Our findings highlight the adaptability of these algorithms to different markers, achievable through both low-dose intraoperative 2D X-ray imaging and standard CT imaging.

Pseudoprogression of Vestibular Schwannoma after Stereotactic Radiosurgery with Cyberknife®: Proposal for New Response Criteria.

(1) Background: Transient increase in volume of vestibular schwannomas (VS) after stereotactic radiosurgery (SRS) is common and complicates differentiation between treatment-related changes (pseudoprogression, PP) and tumor recurrence (progressive disease, PD). (2) Methods: Patients with unilateral VS (n = 63) underwent single fraction robotic-guided SRS. Volume changes were classified according to existing RANO criteria. A new response type, PP, with a >20% transient increase in volume was defined and divided into early (within the first 12 months) and late (>12 months) occurrence. (3) Results: The median age was 56 (range: 20-82) years, the median initial tumor volume was 1.5 (range: 0.1-8.6) cm3. The median radiological and clinical follow-up time was 66 (range: 24-103) months. Partial response was observed in 36% (n = 23), stable disease in 35% (n = 22) and PP in 29% (n = 18) of patients. The latter occurred early (16%, n = 10) or late (13%, n = 8). Using these criteria, no case of PD was observed. (4) Conclusion: Any volume increase after SRS for vs. assumed to be PD turned out to be early or late PP. Therefore, we propose modifying RANO criteria for SRS of VS, which may affect the management of vs. during follow-up in favor of further observation.

Use of dose-area product to assess plan quality in robotic radiosurgery.

PURPOSE: In robotic stereotactic radiosurgery (SRS), optimal selection of collimators from a set of fixed cones must be determined manually by trial and error. A unique and uniformly scaled metric to characterize plan quality could help identify Pareto-efficient treatment plans. METHODS: The concept of dose-area product (DAP) was used to define a measure (DAPratio) of the targeting efficiency of a set of beams by relating the integral DAP of the beams to the mean dose achieved in the target volume. In a retrospective study of five clinical cases of brain metastases with representative target volumes (range: 0.5-5.68 ml) and 121 treatment plans with all possible collimator choices, the DAPratio was determined along with other plan metrics (conformity index CI, gradient index R50%, treatment time, total number of monitor units TotalMU, radiotoxicity index f12, and energy efficiency index η50%), and the respective Spearman's rank correlation coefficients were calculated. The ability of DAPratio to determine Pareto efficiency for collimator selection at DAPratio < 1 and DAPratio < 0.9 was tested using scatter plots. RESULTS: The DAPratio for all plans was on average 0.95 ±â€¯0.13 (range: 0.61-1.31). Only the variance of the DAPratio was strongly dependent on the number of collimators. For each target, there was a strong or very strong correlation of DAPratio with all other metrics of plan quality. Only for R50% and η50% was there a moderate correlation with DAPratio for the plans of all targets combined, as R50% and η50% strongly depended on target size. Optimal treatment plans with CI, R50%, f12, and η50% close to 1 were clearly associated with DAPratio < 1, and plans with DAPratio < 0.9 were even superior, but at the cost of longer treatment times and higher total monitor units. CONCLUSIONS: The newly defined DAPratio has been demonstrated to be a metric that characterizes the target efficiency of a set of beams in robotic SRS in one single and uniformly scaled number. A DAPratio < 1 indicates Pareto efficiency. The trade-off between plan quality on the one hand and short treatment time or low total monitor units on the other hand is also represented by DAPratio.

Impact of prescription isodose level and collimator selection on dose homogeneity and plan quality in robotic radiosurgery.

PURPOSE: In stereotactic radiosurgery (SRS), prescription isodoses and resulting dose homogeneities vary widely across different platforms and clinical entities. Our goal was to investigate the physical limitations of generating dose distributions with an intended level of homogeneity in robotic SRS. METHODS: Treatment plans for non-isocentric irradiation of 4 spherical phantom targets (volume 0.27-7.70 ml) and 4 clinical targets (volume 0.50-5.70 ml) were calculated using Sequential (phantom) or VOLOTM (clinical) optimizers (Accuray, Sunnyvale, CA, USA). Dose conformity, volume of 12 Gy isodose (V12Gy) as a measure for dose gradient, and treatment time were recorded for different prescribed isodose levels (PILs) and collimator settings. In addition, isocentric irradiation of phantom targets was examined, with dose homogeneity modified by using different collimator sizes. RESULTS: Dose conformity was generally high (nCI ≤ 1.25) and varied little with PIL. For all targets and collimator sets, V12Gy was highest for PIL ≥ 80% and lowest for PIL ≤ 65%. The impact of PIL on V12Gy was highest for isocentric irradiation and lowest for clinical targets (VOLOTM optimization). The variability of V12Gy as a function of collimator selection was significantly higher than that of PIL. V12Gy and treatment time were negatively correlated. Plans utilizing a single collimator with a diameter in the range of 70-80% of the target diameter were fastest, but showed the strongest dependence on PIL. CONCLUSION: Inhomogeneous dose distributions with PIL ≤ 70% can be used to minimize dose to normal tissue. PIL ≥ 90% is associated with a marked and significant increase in off-target dose exposure. Careful selection of collimators during planning is even more important.

DiODe v2: Unambiguous and Fully-Automated Detection of Directional DBS Lead Orientation.

Directional deep brain stimulation (DBS) leads are now widely used, but the orientation of directional leads needs to be taken into account when relating DBS to neuroanatomy. Methods that can reliably and unambiguously determine the orientation of directional DBS leads are needed. In this study, we provide an enhanced algorithm that determines the orientation of directional DBS leads from postoperative CT scans. To resolve the ambiguity of symmetric CT artifacts, which in the past, limited the orientation detection to two possible solutions, we retrospectively evaluated four different methods in 150 Cartesia™ directional leads, for which the true solution was known from additional X-ray images. The method based on shifts of the center of mass (COM) of the directional marker compared to its expected geometric center correctly resolved the ambiguity in 100% of cases. In conclusion, the DiODe v2 algorithm provides an open-source, fully automated solution for determining the orientation of directional DBS leads.

Assessing Associations of Synovial Perfusion, Cartilage Quality, and Outcome in Rheumatoid Arthritis Using Dynamic Contrast-enhanced Magnetic Resonance Imaging.

OBJECTIVE: To assess associations of synovial perfusion, cartilage quality, and outcome in rheumatoid arthritis (RA). METHODS: Synovial perfusion and cartilage quality were assessed by dynamic contrast-enhanced magnetic resonance imaging in metacarpophalangeal joints of 28 treatment-naive patients with RA at baseline and at 3 and 6 months after methotrexate. Analysis was by linear mixed modeling. RESULTS: Synovial perfusion variables were associated with remission (p < 0.05) and cartilage quality (p < 0.004). Maximum synovial enhancement was associated to European League Against Rheumatism response (p < 0.05). Synovial perfusion improved in nonresponders over time (p < 0.05). CONCLUSION: Synovial perfusion relates to remission, response, and cartilage quality in a cohort of therapy-naive patients with early RA.

MRI identifies biochemical alterations of intervertebral discs in patients with low back pain and radiculopathy.

KEY POINTS: • Molecular intervertebral disc damage was associated with LBP and radiculopathy.• Patients with radiculopathy and LBP demonstrated a depletion of gagCEST values compared with healthy controls.• GagCEST imaging may be a non-invasive tool for investigation of degeneration processes of lumbar intervertebral discs (IVDs). GagCEST imaging may be an imaging biomarker for biochemical IVD alterations.

Prevention of the progressive biochemical cartilage destruction under methotrexate therapy in early rheumatoid arthritis.

OBJECTIVES: The aim of the study was to investigate biochemical cartilage composition under methotrexate (MTX) therapy and to intra-individually assess the impact of inflammation severity on cartilage composition by using dGEMRIC MRI in patients with early rheumatoid arthritis (eRA). METHODS: dGEMRIC of MCP joints of the index and middle finger of 28 patients from the AthroMark cohort were examined prior to MTX-therapy as well as after 3 and 6 month. OMERACT RA MRI score and clinical parameters (CRP and DAS28) were registered at any time point. Each patient's second and third MCP joints were dichotomised into the joint with more severe synovitis versus the joint with less severe synovitis according to the RAMRIS synovitis subscore. RESULTS: MCP joints with more severe synovitis ('bad joints') demonstrated significantly lower dGEMRIC values compared to MCP joints with less severe synovitis ('good joints') at time-points 0 and 3 months (p=0.002; p=0.019, respectively). After 6 months of MTX therapy no significant difference of dGEMRIC index was found between good and bad joint (p=0.086). CONCLUSIONS: Under MTX therapy, biochemical cartilage integrity remains stable; no further cartilage destruction occurred if patients were treated early in the course of the disease. In addition, six months of MTX therapy triggered an alignment of dGEMRIC index of MCP joints with initially severe synovitis and less severe synovitis in an intra-individual assessment. This underlines the importance of an early treatment in eRA to reduce further cartilage damage of the inflamed joints.

Differences of radiocarpal cartilage alterations in arthritis and osteoarthritis using morphological and biochemical magnetic resonance imaging without gadolinium-based contrast agent administration.

OBJECTIVES: To identify differences of radiocarpal cartilage alterations in osteoarthritis and arthritis using multiparametrical magnetic resonance imaging (MRI) comprising morphological and biochemical sequences without gadolinium-based contrast agent administration. METHODS: In this prospective study, multiparametrical MRI of the radiocarpal cartilage was performed in 47 participants (mean age, 46.6 ± 17.6 years; min., 20 years; max., 79 years) on a 3 Tesla MRI. The cohort consisted of 11 patients suffering from arthritis, 10 patients with osteoarthritis, 14 patients after distal radius fracture, and 12 healthy volunteers. The radiocarpal cartilage was assessed using morphological (DESS, TrueFISP) and biochemical (T2*) MRI sequences without the application of intravenous contrast agent. The modified Outerbridge classification system for morphological and region-of-interest analyses for biochemical analysis was applied to assess the degree of cartilage damage in each patient before data were statistically tested for significant difference between the groups using a post hoc Tukey test. RESULTS: In morphological imaging, cartilage damage was significantly more frequent in arthritis and osteoarthritis than in healthy volunteers (DESS: p = 0.01, p = 0.0004; TrueFISP: p = 0.02, p = 0.0001). In T2* imaging, patients with osteoarthritis showed higher cartilage damage compared to patients with arthritis (p = 0.01). CONCLUSION: With multiparametrical MRI, it is possible to identify differences of radiocarpal cartilage alterations of patients with arthritis and osteoarthritis using the combination of morphological and biochemical MR imaging of the radiocarpal cartilage without the application of contrast agent. Multiparametrical MRI without the usage of contrast agent may be a potential tool helping to distinguish both entities. KEY POINTS: • Multiparametrical MRI with morphological and biochemical sequences allows the differentiation of patients with arthritis and osteoarthritis. • High-resolution MRI of radiocarpal cartilage is possible without administration of contrast agent.

Age-related apparent diffusion coefficients of lumbar vertebrae in healthy children at 1.5 T.

BACKGROUND: Diffusion-weighted magnetic resonance imaging with apparent diffusion coefficient (ADC) calculation is important for detecting bone marrow pathologies. OBJECTIVE: To investigate age-related differences of lumbar vertebral body ADC to establish normal values for healthy children. MATERIALS AND METHODS: Forty-nine healthy children without any history of oncological or hematological diseases (10.2±4.7 years, range: 0-20 years) were included in this retrospective study. All magnetic resonance imaging (MRI) examinations were performed at 1.5 T and with similar scan parameters. The diffusion-weighted sequences were performed with b values of 50, 400 and 800 s/mm2. ADC values were measured by placing regions of interest at three different levels within each lumbar vertebral body (L1 to L5). ADC values were analyzed for different age groups (0-2 years, 3-6 years, 7-11 years, 12-14 years, 15-20 years), for each vertebral and intravertebral level. RESULTS: The mean ADC of the whole study group was 0.60±0.09 × 10-3 mm2/s. Children between the ages of 12 and 14 years had significantly higher ADC compared to the other age groups (P≤0.0003). ADC values were significantly higher in the 1st lumbar vertebral body compared to the other levels of the lumbar spine (P<0.005) with the exception of L5, and in the upper third of the vertebral bodies compared to the middle or lower thirds (P≤0.003). CONCLUSION: The age-, vertebral- and intravertebral level-dependent differences in ADC suggest a varying composition and cellularity in different age groups and in different locations.

Glycosaminoglycan Chemical Exchange Saturation Transfer of Lumbar Intervertebral Discs in Healthy Volunteers.

STUDY DESIGN: Evaluation of a new quantitative imaging technique in a prospective study design. OBJECTIVE: To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVDs) in healthy volunteers with chemical exchange saturation transfer (CEST). SUMMARY OF BACKGROUND DATA: Biochemical alterations of lumbar discs are present before the appearance of morphological changes. GAG loss plays a central role in these degenerative processes. METHODS: Lumbar intervertebral discs of healthy controls (26 women, 22 men; mean age 31 ±â€Š8 years; range: 21-49 years) without lumbar back pain were examined at a 3 Tesla magnetic resonance imaging (MRI) scanner in this prospective study. None of the participants were overweight or had previous surgery of the lumbar spine. The MRI protocol included standard morphological, sagittal and transversal T2-weighted (T2w) images to assess Pfirrmann score and to detect disc disorders according to the Combined Task Force classification of five lumbar IVDs (L1 to S1). A prototype glycosaminoglycan chemical exchange saturation transfer (gagCEST) sequence was applied to measure GAG content of the nucleus pulposus (NP) and annulus fibrosus (AF) by identifying the magnetization transfer asymmetry ratio (MTRasym) in a region-of-interest analysis. Morphological and biochemical imaging analysis were statistically tested for quantitative differences between different grades of IVD degeneration and disc disorders. RESULTS: gagCEST values of NP demonstrated a significant negative correlation with morphological Pfirrmann score (r = -0.562; P < 0.0001). The MTRasym values were higher in non-degenerative lumbar IVDs (Pfirrmann 1-2) compared with degenerative lumbar discs (Pfirrmann 3-5; 2.92% ±â€Š1.42% vs. 0.78% ±â€Š1.38%; P < 0.0001). The MTRasym values of NP were significantly higher in normal appearing discs compared with herniated IVDs (2.83% ±â€Š1.52% vs. 1.55% ±â€Š1.61%; P < 0.0001). We found a significant negative correlation between gagCEST values and the graduation of disc herniation (r = -0.372; P < 0.0001). CONCLUSION: Biochemical imaging with gagCEST distinguished morphologically degenerative from non-degenerative lumbar IVDs (in NP and AF) of healthy volunteers at a clinical 3T-MRI system. The depletion of GAG content in degenerative lumbar discs correlated significantly with the morphological disc classification. We could demonstrate that disc disorders, such as protrusion and extrusion, were accompanied by lower GAG content. LEVEL OF EVIDENCE: 2.

An interaction of a NR3C1 polymorphism and antenatal solar activity impacts both hippocampus volume and neuroticism in adulthood.

The investigation of the interaction of genes and environment in the context of mental health and personality yields important new insights for a better understanding of human nature. Both antenatal and postnatal environmental factors have been considered as potential modulators of genetic activity. Antenatally, especially smoking or alcohol drinking habits of the mother dramatically influence the health of the child during pregnancy and even later on in life. In the present study we would like to introduce a more "distant" factor that is not under the control of the becoming mother but that nevertheless plays a potential role for the health of the unborn child later on in adulthood. Here, we retrospectively investigate the influence of solar activity (while the child is still in the uterus of the becoming mother) on brain structure (with a focus on hippocampus and amygdala volume) and personality in adulthood. We observe an interaction of a genetic variant (rs41423247) of the glucocorticoid receptor gene (NR3C1) and solar activity in the first trimester after conception on both hippocampal volume and the personality trait neuroticism in adulthood in N = 254 participants. The NR3C1 gene is the focus of interest, because of its influence on the hypothalamic-pituitary-adrenal (HPA) axis and negative emotionality. Carriers of the CC variant of rs41423247 grown in the womb under the influence of high sun radiation (high solar activity) show both the highest hippocampal volume in the left hemisphere and lowest neuroticism scores. The present findings should encourage researchers in psychology and psychiatry to include also environmental influences such as solar activity besides genetics to better understand the etiogenesis of psychiatric disorders.