Prophylactic anticoagulation to prevent venous thromboembolism in traumatic intracranial hemorrhage: a decision analysis

Abstract Introduction Patients with intracranial hemorrhage due to traumatic brain injury are at high risk of developing venous thromboembolism including deep vein thrombosis (DVT) and pulmonary embolism (PE). Thus, there is a trade-off between the risks of progression of intracranial hemorrhage (ICH) versus reduction of DVT/PE with the use of prophylactic anticoagulation. Using decision analysis modeling techniques, we developed a model for examining this trade-off for trauma patients with documented ICH. Methods The decision node involved the choice to administer or to withhold low molecular weight heparin (LMWH) anticoagulation prophylaxis at 24 hours. Advantages of withholding therapy were decreased risk of ICH progression (death, disabling neurologic deficit, non-disabling neurologic deficit), and decreased risk of systemic bleeding complications (death, massive bleed). The associated disadvantage was greater risk of developing DVT/PE or death. Probabilities for each outcome were derived from natural history studies and randomized controlled trials when available. Utilities were obtained from accepted databases and previous studies. Results The expected value associated with withholding anticoagulation prophylaxis was similar (0.90) to that associated with the LMWH strategy (0.89). Only two threshold values were encountered in one-way sensitivity analyses. If the effectiveness of LMWH at preventing DVT exceeded 80% (range from literature 33% to 82%) our model favoured this therapy. Similarly, our model favoured use of LMWH if this therapy increased the risk of ICH progression by no more than 5% above the baseline risk. Conclusions Our model showed no clear advantage to providing or withholding anticoagulant prophylaxis for DVT/PE prevention at 24 hours after traumatic brain injury associated with ICH. Therefore randomized controlled trials are justifiable and needed to guide clinicians

Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases

The use of radiotherapy, either in the form of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), remains the cornerstone for the treatment of brain metastases (BM). As the survival of patients with BM is being prolonged, due to improved systemic therapy (i.e., for better extra-cranial control) and increased use of SRS (i.e., for improved intra-cranial control), patients are clinically manifesting late effects of radiotherapy. One of these late effects is radiation necrosis (RN). Unfortunately, symptomatic RN is notoriously hard to diagnose and manage. The features of RN overlap considerably with tumor recurrence, and misdiagnosing RN as tumor recurrence may lead to deleterious treatment which may cause detrimental effects to the patient. In this review, we will explore the pathophysiology of RN, risk factors for its development, and the strategies to evaluate and manage RN

Chemical exchange saturation transfer MRI in central nervous system tumours on a 1.5 T MR-Linac

Purpose: To describe the implementation and initial results of using Chemical Exchange Saturation Transfer (CEST) for monitoring patients with central nervous system (CNS) tumours treated using a 1.5 tesla MR-guided radiotherapy system. Methods: CNS patients were treated with up to 30 fractions (total dose up to 60 Gy) using a 1.5 T Elekta Unity MR-Linac. CEST scans were obtained in 54 subjects at one or more time points during treatment. CEST metrics, including the amide magnetization transfer ratio (MTRAmide), nuclear Overhauser effect (NOE) MTR (MTRNOE) and asymmetry, were quantified in phantoms and CNS patients. The signal was investigated between tumour and white matter, across time, and across disease categories including high- and low-grade tumours. Results: The gross tumour volume (GTV) exhibited lower MTRAmide and MTRNOE and higher asymmetry compared to contralateral normal appearing white matter. Signal changes in the GTV during fractionated radiotherapy were observed. There were differences between high- and low-grade tumours, with higher CEST asymmetry associated with higher grade disease. Conclusion: CEST MRI using a 1.5 T MR-Linac was demonstrated to be feasible for in vivo imaging of CNS tumours. CEST images showed tumour/white-matter contrast, temporal CEST signal changes, and associations with tumour grade. These results show promise for the eventual goal of using metabolic imaging to inform the design of adaptive radiotherapy protocols

Cost-effectiveness Analysis of Core Decompression

Core decompression is widely used to treat the early stages of osteonecrosis of the hip. The purpose of this analysis is to assist orthopedic surgeons in judging whether currently available data support the use of core decompression as cost-effective. A decision model was created for the treatment of osteonecrosis of the femoral head. Literature review was used to identify possible outcomes and their probability after initial treatment with either observation or core decompression. This model demonstrates core decompression must delay the need for total hip arthroplasty for a minimum of 5 years to maintain an incremental cost-effectiveness ratio lower than 50,000 dollars per quality-adjusted life year gained. Treatment options with ratios higher than 50,000 dollars per quality-adjusted life year are generally considered to have limited cost-effectiveness. This study demonstrates that core decompression has the potential to be a highly cost-effective alternative if it is leads to a delay in the need for total hip arthroplasty of 5 years or longer

Cardiac Tissue Characterization Following Myocardial Infarction Using Magnetic Resonance Imaging

This thesis describes the development of new magnetic resonance imaging (MRI) methods to characterize cardiac tissue with myocardial infarction (MI). Wall motion imaging (for visualizing myocardial contraction) and viability imaging (to identify MI) are two components of cardiac tissue characterization used for prognosis and treatment planning. MRI-based wall motion and viability methods are considered the gold standard in imaging, and characterization of MRI viability images has been correlated with inducibility for ventricular tachycardia (VT). However, viability imaging with MRI has limitations such as difficulty visualizing the blood-infarct border. Wall motion and viability images are acquired separately, each requiring cardiac gating and breath holds, leading to long scan times. A novel multi-contrast delayed enhancement (MCDE) sequence was developed that simultaneously acquires wall motion and viability images. In a patient study, the MCDE sequence was demonstrated to provide improved visualization of MI compared to the conventional inversion-recovery gradient echo (IR-GRE) sequence, particularly for small infarcts adjacent to the blood pool. MCDE images also provided accurate wall motion images that could be used to calculate the left ventricular ejection fraction. An image processing algorithm was developed to analyze MCDE images to segment and classify the infarct gray zone, which is hypothesized to represent heterogeneous infarct responsible for causing VT. In a study of 15 patients with MI, the MCDE-derived gray zone was shown to be less sensitive to image noise than the IR-GRE-derived gray zone, and did not require manual contours of the blood pool which contributes to additional variability in the IR-GRE gray zone analysis. Finally, a real-time delayed enhancement (RT-DE) method was developed to provide black-blood viability images without requiring cardiac gating or breath holds. RT-DE imaging was shown to have a high sensitivity for detecting MI in a study of 23 patients. The methods described in this thesis help expand the patient population that can undergo a cardiac viability exam and help improve the visualization of myocardial infarct. Further modifications in the pulse sequences to improve the temporal and spatial resolutions are proposed with the goal of predicting and guiding treatment of ventricular tachycardia resulting from myocardial infarct.Ph