Management Of Brain Tumors Research Articles

Immunohistochemical Characterization of Procaspase-3 Overexpression as a Druggable Target With PAC-1, a Procaspase-3 Activator, in Canine and Human Brain Cancers.

Gliomas and meningiomas are the most common brain neoplasms affecting both humans and canines, and identifying druggable targets conserved across multiple brain cancer histologies and comparative species could broadly improve treatment outcomes. While satisfactory cure rates for low grade, non-invasive brain cancers are achievable with conventional therapies including surgery and radiation, the management of non-resectable or recurrent brain tumors remains problematic and necessitates the discovery of novel therapies that could be accelerated through a comparative approach, such as the inclusion of pet dogs with naturally-occurring brain cancers. Evidence supports procaspase-3 as a druggable brain cancer target with PAC-1, a pro-apoptotic, small molecule activator of procaspase-3 that crosses the blood-brain barrier. Procaspase-3 is frequently overexpressed in malignantly transformed tissues and provides a preferential target for inducing cancer cell apoptosis. While preliminary evidence supports procaspase-3 as a viable target in preclinical models, with PAC-1 demonstrating activity in rodent models and dogs with spontaneous brain tumors, the broader applicability of procaspase-3 as a target in human brain cancers, as well as the comparability of procaspase-3 expressions between differing species, requires further investigation. As such, a large-scale validation of procaspase-3 as a druggable target was undertaken across 651 human and canine brain tumors. Relative to normal brain tissues, procaspase-3 was overexpressed in histologically diverse cancerous brain tissues, supporting procaspase-3 as a broad and conserved therapeutic target. Additionally, procaspase-3 expressing glioma and meningioma cell lines were sensitive to the apoptotic effects of PAC-1 at biologically relevant exposures achievable in cancer patients. Importantly, the clinical relevance of procaspase-3 as a potential prognostic variable was demonstrated in human astrocytomas of variable histologic grades and associated clinical outcomes, whereby tumoral procaspase-3 expression was negatively correlated with survival; findings which suggest that PAC-1 might provide the greatest benefit for patients with the most guarded prognoses.

Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial.

Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS). We used gold nanoparticles due to their surface plasmon effect that enables their sensitive and microscopic resolution detection using the SERS technique. Raman microscopy of the resected tumors showed heterogeneous EPR of nanoparticles into oligodendrogliomas and meningiomas of different grades, without any detectable traces in necrotic parts of the tumors or normal brain. Raman observations were confirmed by scanning electron microscopy (SEM) and X-ray elemental analyses, which enabled localization of individual nanoparticles embedded in tumor tissues. Our results demonstrate nanoparticles' EPR and its variations in clinically relevant, spontaneous brain tumors. Such heterogeneities should be considered alongside routine preoperative imaging and histopathological analyses in order to accelerate clinical management of brain tumors using nanomedicine approaches.

Progesterone Is More Effective Than Dexamethasone in Prolonging Overall Survival and Preserving Neurologic Function in Experimental Animals with Orthotopic Glioblastoma Allografts

Dexamethasone (DEXA) has been widely used in the management of peritumoral brain edema. DEXA, however, has many systemic side effects and can interact negatively with glioma therapy. Progesterone (PROG), however, is a well-tolerated and readily accessible anti-inflammatory and antiedema agent, with potent neuroprotective properties. We investigated whether PROG could serve as a viable alternative to DEXA in the management of peritumoral brain edema. We used an orthotopic C6 glioblastoma model with male Sprague-Dawley rats. Tumor grafts were allowed to grow for 14 days before drug treatment with DEXA 1 mg/kg, PROG 10 mg/kg, or PROG 20 mg/kg for 5 consecutive days. The overall animal survival and neurologic function were evaluated. Mechanistic studies on blood-brain barrier permeability and angiogenic responses were performed on the exvivo tumor grafts. We found that all drug treatments prolonged overall survival to different extents. PROG 10 mg led to significantly longer survival and better preservation of neurologic function and body weight. The blood-brain barrier permeability was better preserved with PROG 10 mg than with DEXA, possibly through downregulation of matrix metalloproteinase-9 and aquaporin-4 expression. Antiangiogenic responses were also observed in the PROGgroup. The present proof-of-concept pilot study has provided novel information on the use of PROG as a corticosteroid-sparing agent in brain tumor management. Further translational and clinical studies are warranted.

Liquid biopsy in central nervous system metastases: a RANO review and proposals for clinical applications.

Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a surrogate for tumor tissue in the management of both primary and secondary brain tumors. Herein we critically review available literature on spinal fluid and plasma circulating tumor cells (CTCs) and cell-free tumor (ctDNA) for diagnosis and monitoring of leptomeningeal and parenchymal brain metastases. We discuss technical issues and propose several potential applications of liquid biopsies in different clinical settings (ie, for initial diagnosis, for assessment during treatment, and for guidance of treatment decisions). Last, ongoing clinical studies on CNS metastases that include liquid biopsies are summarized, and recommendations for future clinical studies are provided.

Letter to the Editor Regarding “Hypnosis-Aided Awake Surgery for the Management of Intrinsic Brain Tumors versus Standard Awake-Asleep-Awake Protocol: A Preliminary, Promising Experience”

Hypnosis could extend the time of Intraoperative Neuropsychological Testing and Brain Mapping in Awake Surgery. A clinical validation for the Hypnosis aided AS (HAs) is still ongoing and further evidences are required. The objective of the present study is to compare two homogeneous cohorts of patients undergoing AS, the first with the aid of the hypnosis and the second according to a standard AS (SAs) protocols. The clinical, radiological and surgical data of two comparable procedures cohorts were retrospectively examined for the present study. All surgeries in Group A were performed with a HAs protocol. Procedures belonging to Group B were performed with a SAs protocol. Endpoints: to compare 1. Incidence of complications in the immediate postoperative period, 2. Clinical and neurological status in the immediate postoperative period and 30 days after surgery, 3. Duration of surgical interventions, 4. Extent of Resection (EOR). The final cohort is composed of 15 procedures; 6 belonging to Group A and 9 to Group B. The different methods outline statistically comparable results from the clinical (Neurological outcomes) both in the postoperative period and one month after surgery and from the surgical point of view (comparable EOR). The incidence of complications is comparable either. The duration of the procedures was significantly longer in HAs group. Hypnosis is a promising approach to increasing the duration of intraoperative “testability” of patients at the price of a longer operative time. A specific professional is needed to induce hypnosis in the difficult intraoperative setting.

Clinical practice guidelines for the management of brain tumours: A rehabilitation perspective.

To critically appraise published clinical practice guidelines (CPGs) for brain tumours, and to synthesize evidence-based recommendations from a rehabilitation perspective. A comprehensive literature search included: health science databases, CPG clearinghouse/developer websites, and grey literature up to March 2018. All brain tumour CPGs that reported systematic methods for evidence search, and clearly defined recommendations supporting evidence for rehabilitation interventions were included. Three authors independently selected potential CPGs and assessed their methodological quality using the Appraisal of Guidelines, Research and Evaluation (AGREE-II) Instrument. Recommendations from included CPGs were categorized from a rehabilitation perspective. Of the 11 CPGs identified, only 2, developed by the National Institute for Health and Clinical Excellence (NICE) and the Australian Cancer Network (ACN), included rehabilitation components for the management of brain tumours. Both CPGs were of moderate quality. The recommendations reported were generic, and only the ACN guidelines provided detailed recommendations for rehabilitation interventions. Both guidelines recommend a comprehensive multi-disciplinary care approach. Detailed comparison, however, was not possible due to inconsistent recommendations, making it difficult to summarize rehabilitative care. Despite rehabilitation being an integral component of the management of brain tumours, only a limited number of CPGs have incorporated recommendations for specific rehabilitation interventions. In order to improve clinical outcomes in this population future CPGs should incorporate rehabilitation interventions.

Preliminary experience in the management of brain and skull-base tumors with microwave ablation; feasibility guided by ultrasound, report from 23 cases.

Background:In surgery involving brain tumors, the use of new tools or equipment that allows for better results and improvement in the quality of life of the patients is mandatory. Microwave ablation (MWA) is a technique that has been used effectively since 1994 in the management of different kinds of tumors. The authors present their surgical experience with 23 cases of brain and skull-base tumors using MWA technique.Methods:In all, 23 cases diagnosed with brain and skull-base tumors are described; all of these were treated with MWA as unique technique as a complement to conventional microsurgical tumor resection. In all cases, ultrasound imaging guidance was used. A thin antenna (caliber 14.5; MedWaves) was positioned through ultrasound images to a central intratumoral area, and then energy was applied for 1–3 min until the temperature sensor in the proximal position of the antenna reached 80–100°C. Through transoperative Doppler ultrasound images and surgical microscopy, changes in the generated ablation were observed. The said ablation led to a decrease in intratumoral blood flow, and the adjacent vascular and cerebral structures were preserved.Results:The application of MWA during brain surgery was regarded as safe in all cases, as no permanent additional neurological deficit was detected. Intratumoral vascular flow was also reduced and tumor resection was facilitated. Likewise, a reduction in tumor volume was noted, and in others in whom the ablation was applied as a single therapy, a progressive destruction of the tumor was observed.Conclusion:MWA can be a useful tool as a single therapy or as a complement to conventional techniques for the surgical resection of brain and skull-base tumors. It was a safe method in all cases, producing a decrease in intratumoral blood flow, and this procedure facilitates the microsurgical resection of the lesion.

Contemporary Surgical Management of Deep-Seated Metastatic Brain Tumors Using Minimally Invasive Approaches.

A subset of metastatic brain tumors occurs in deep-seated locations. Accessing and resecting these lesions can be associated with significant morbidity because it involves large craniotomies, extensive white matter dissection, prolonged retraction, and risk of inadvertent tissue injury. As a result, only palliative treatment options are typically offered for these lesions including observation, needle biopsies, and/or radiation therapy. With the development of new surgical tools and techniques, minimally invasive techniques have allowed for the treatment of these lesions previously associated with significant morbidity. These minimally invasive techniques include laser interstitial thermal therapy and channel-based resections.

The Latin American Brain Tumor Board teleconference: results of a web-based survey to evaluate participant experience utilizing this resource.

The Latin American Brain Tumor Board (LATB) is a weekly teleconference connecting pediatric neuro-oncologists from referral centers in high-income countries with pediatric subspecialists from 20 Latin American countries since 2013. This survey explored the participants' experience utilizing this resource. A cross-sectional electronic questionnaire was distributed to 159 participants through email and Cure4Kids. Ninety-five respondents (60%) from all the participating countries completed the survey. Sixty-one reported frequent-attendance (≥ 1 per month), 23 reported infrequent-attendance (< 1 per month), and 11 never participated. The most frequently reported attendance-barriers were the subspecialist's workload (64%), the timing of the teleconference (38%), and Internet connectivity problems (29%). Subspecialist's workload was more frequently reported as a barrier compared with other barriers, in both the frequent- and infrequent-attendance groups (p < 0.05), with the exception of the timing of the meeting in the infrequent-attendance group. More than 80% of attendees found the frequency and duration of the teleconference were sufficient. Utilizing Spanish as the primary language was reported to enhance the recommendations by 93% of the attendees. Moreover, 84% reported that the recommendations (almost) always fit the local circumstances. Furthermore, 99% of attendees found the teleconference provided a continuing medical education opportunity. Finally, 96% of attendees (almost) always found that the provided recommendations helped to improve the outcomes/quality of life of the patients. The LATB teleconference provided a valuable tool for the management of pediatric brain tumors in Latin America as it provided a feasible and easy to access continued medical education opportunity for the participants.

Technical Advances in Radiation Therapy for Brain Tumors.

Radiation therapy plays a critical role in the management of brain tumors. Recent advances in radiation techniques include the use of intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and stereotactic radiosurgery (SRS). All of these techniques allow the delivery of higher radiation doses to the target volume, at the same time reducing the risk of toxicity to normal tissues as compared with conventional 3D conformal radiotherapy (3D-CRT). Proton therapy may represent a treatment alternative to photon irradiation, due to the more favorable dose distribution to the target volume. This review summarizes current developments in radiation therapy and their clinical impact on the management of patients with brain tumors.

Targeting Brain Tumors with Nanomedicines: Overcoming Blood Brain Barrier Challenges.

This review elucidates ongoing research, which show improved delivery of anticancer drugs alone and/ or enclosed in carriers collectively called nanomedicines to cross the BBB/ BTB to kill tumor cells and impact patient survival. We highlighted various advances in understanding the mechanism of BTB function that has an impact on anticancer therapeutics delivery. We discussed latest breakthroughs in developing pharmaceutical strategies, including nanomedicines and delivering them across BTB for brain tumor management and treatment. We performed an extensive literature search and highlighted important studies on the regulation of BTB permeability with respect to nanotech-based nanomedicines for targeted treatment of brain tumors. We have reviewed research articles that describe the development of specialized molecules and nanospheres, which carry payload of anticancer agents to brain tumor cells across the BBB/ BTB and avoid drug efflux systems. We highlighted research on the identification and development of targeted anti-cancer drug delivery to brain tumors. In addition, we discussed multimeric molecular therapeutics and nanomedicines that were encapsulated in nanospheres for treatment and monitoring of brain tumors. In this context, we quoted our research on large conductance calcium-activated potassium channels (BKCa) and ATP-dependent potassium channels (KATP) as portals of enhanced antineoplastic drugs delivery. We showed that several innovative drug delivery agents such as liposomes, polymeric nanoparticles, dendrimers and many such tools can be utilized to improve anticancer drugs and nanomedicines across the BTB to reach brain tumor cells. This review might interest both academic and drug company scientists involved in drug delivery to brain tumors. We further seek to present evidence that BTB modulators can be clinically developed as combination drug or/ and as stand-alone anticancer drugs. Eventually, it is expected that unrelenting effort from the scientific community in developing novel drug delivery methods should increase the survival rate of brain tumor patients, which is dismally low presently.

Diagnosis and Management of Brain Tumors in Children

Brain tumors are the second most common malignancy and the most common solid tumors found in childhood. During 11 months 19 patients with brain tumors were hospitalized at the Department of Child Health, Dr. Cipto Mangunkusurno Hospital, Jakarta, 10 of them were males. The youngest patient was 5 months old and the oldest was 13 years old. The important signs and symptoms in establishing diagnosis were the non-localizing signs and symptoms, i.e., nausea and vomiting. The most frequent localizing signs and symptoms were papilledema, cranial nerves palsy, ataxia and incoordination, hemiparesis, visual disturbances, and optic atrophy. Focal seizures were rare.&#x0D; Most of the tumors were in infratentorial region, and metastatic tumors were rare. The mortality of this series was high due to the severity of the disease. The most frequent of tumors are astrocytomas and medulloblastomas.

WHO-Klassifikation der Hirntumoren 2016: radiologisch relevante Neuerungen

AbstractRadiologists play a key role in brain tumor diagnosis and management and must stay abreast of developments in the field to advance patient care and communicate with other health care providers. In 2016, the World Health Organization (WHO) released an update to its brain tumor classification system that included numerous significant changes. Several previously recognized brain tumor diagnoses, such as oligoastrocytoma, primitive neuroectodermal tumor, and gliomatosis cerebri, were redefined or eliminated altogether. Conversely, multiple new entities were recognized, including diffuse leptomeningeal glioneuronal tumor and multinodular and vacuolating tumor of the cerebrum. The glioma category has been significantly reorganized, with several infiltrating gliomas in children and adults now defined by genetic features for the first time. These changes were driven by increased understanding of important genetic factors that directly impact tumorigenesis and influence patient care. The increased emphasis on genetic factors in brain tumor diagnosis has important implications for radiology, as we now have tools that allow us to evaluate some of these alterations directly, such as the identification of 2-hydroxyglutarate within infiltrating gliomas harboring mutations in the genes for the isocitrate dehydrogenases. For other tumors, such as medulloblastoma, imaging can demonstrate characteristic patterns that correlate with particular disease subtypes. The purpose of this article is to review the changes to the WHO brain tumor classification system that are most pertinent to radiologists.

Intensity Modulated Radiation Therapy Versus Volumetric Arc Radiation Therapy in the Treatment of Glioblastoma—Does Clinical Benefit Follow Dosimetric Advantage?

PurposeVolumetric modulated arc therapy (VMAT) has been shown by multiple planning studies to hold dosimetric advantages over intensity modulated radiation therapy (IMRT) in the management of brain tumors, including glioblastoma (GBM). Although promising, the clinical impact of these findings has not been fully elucidated. Methods and MaterialsWe retrospectively reviewed consecutive patients with a pathologic-confirmed diagnosis of GBM who were treated between 2014 and 2015, a period that encompassed the transition from IMRT to VMAT at a single institution. After surgery, radiation with VMAT consisted of 2 to 3 coplanar arcs with or without an additional noncoplanar arc or IMRT with 5 to 6 gantry angles with concurrent and adjuvant temozolomide. Actuarial analyses were performed using the Kaplan Meier method. ResultsA total of 88 patients treated with IMRT (n = 45) and VMAT (n = 43) were identified. Patients were similar in terms of age, sex, performance status, extent of resection, and the high dose target volume. At a median follow-up time of 27 months (range, .7-32.3 months), the overall survival, freedom from progression, and freedom from new or worsening toxicity rates were not different between the 2 treatment groups (log-rank: P = .33; .87; and .23, respectively). There was no difference in incidences of alopecia, erythema, nausea, worsening or new onset fatigue, or headache during radiation, or temozolomide dose reduction for thrombocytopenia or neutropenia (all P > .05). Patterns of failure were different with more out of field failures in the IMRT group (P = .02). The mean time of treatment (TOT) was significantly reduced by 29% (P < .01) with VMAT (mean TOT: 10.3 minutes) compared with IMRT (mean TOT: 14.6 minutes). ConclusionsFor GBM, treatment with VMAT results in similar oncologic and toxicity outcomes compared with IMRT and may improve resource utilization by reducing TOT. VMAT should be considered a potential radiation modality for patients with GBM.

P01.165 A prospective study investigating the Impact Of MultidiscipliNarY tumor Board in brain tumor management: the OMNYBuS Project

P01.165 A prospective study investigating the Impact Of MultidiscipliNarY tumor Board in brain tumor management: the OMNYBuS Project

340 Convection-Enhanced Delivery of Macromolecules to the Brain Using Electrokinetic Transport

Electrokinetic transport in brain tissue represents the movement of molecules due to an applied electric field and the interplay between the electrophoretic and electroosmotic velocities that are developed. This dissertation provides a framework for understanding electrokinetic transport and how it may be utilized for short-distance ejections, relevant to capillary iontophoresis, and long-distance infusions, for the clinical management of malignant brain tumors as a novel convection-enhanced drug delivery system.In particular, electrokinetic transport was first analyzed in a series of poly(acrylamide-co-acrylic acid) hydrogels that demonstrated varying electroosmotic velocities. Moreover, a hydrogel was synthesized to mimic the electrokinetic properties of organotypic hippocampal slice cultures (OHSC), as a surrogate for brain tissue. Short- and long-distance capillary infusions of molecules into the hydrogels and OHSC provided a framework to understand the relevant phenomena, such as the effect of varying the capillary tip size, applied electrical current, ζ-potential of the capillary or the outside matrix, infusion time, tortuosity, and properties of the solute (including molecular weight and electrophoretic mobility). Control of the directional transport of molecules was also demonstrated over a distance of several hundred micrometers to millimeters. Finally, electrokinetic infusions were conducted in vivo in the adult rat brain, with results compared to those of pressure-driven infusions.The experiments and results described in this dissertation provide a foundation for further development, by presenting a methodical means to increase the ejection profile and attain clinically relevant penetration distances while minimizing adverse effects to the brain tissue, including from the electric field itself. The rate of electrokinetic transport is greater than the rate of diffusion, and therefore it represents a novel form of convection-enhanced drug delivery system.

Update on amino acid PET of brain tumours

The aim of this study was to give an update on the emerging role of PET using radiolabelled amino acids in the diagnostic workup and management of patients with cerebral gliomas and brain metastases. Numerous studies have demonstrated the potential of PET using radiolabelled amino acids for differential diagnosis of brain tumours, delineation of tumour extent for treatment planning and biopsy guidance, differentiation between tumour progression and recurrence versus treatment-related changes, and for monitoring of therapy. The Response Assessment in Neuro-Oncology (RANO) working group - an international effort to develop new standardized response criteria for clinical trials in brain tumours - has recently recommended the use of amino acid PET imaging for brain tumour management in addition to MRI at every stage of disease. With the introduction of F-18 labelled amino acids, a broader clinical application has become possible, but is still hampered by the lack of regulatory approval and of reimbursement in many countries. PET using radiolabelled amino acids is a rapidly evolving method that can significantly enhance the diagnostic value of MRI in brain tumours. Current developments suggest that this imaging technique will become an indispensable tool in neuro-oncological centres in the near future.

Frequency of gross total resection in intra-axial brain tumors with help of neuronavigation

Background: Neuronavigation has become a ubiquitous tool in the surgical management of brain tumors. Neuronavigation is most useful as an adjunct to other brain-mapping techniques such as awake mapping and electrocorticography in the resection of lesions within eloquent motor and language areas. Neuronavigation is also commonly used in skull base tumors, especially for planning an operative trajectory in regions containing vital neurovascular structures and may be used for cerebrovascular surgery. The current study was planned to determine the frequency of gross total resection in intra-axial brain tumors with the help of neuronavigation.Methods: This cross-sectional study was carried out in the Department of Neurosurgery, Nishtar Medical College and Hospital, Multan, from September 2014 to March 2015. After approval from institutional ethical committee, seventy-seven patients fulfilling the inclusion criteria were selected from the patient admitted in the Neurosurgical Department through the Out-Patient Department and patients referred from other departments. After thorough counseling with the patient and his/her relatives, informed consent for procedure was taken.Results: Total 78 patients were included in the study. Out of these 78 (100%), 41 (52.6%) were male and 37 (47.4%) were female. As concern to the outcome variable (gross total resection), out of 78 (100%), in 61 (78.2%) patients gross total resection was present. On cross tabulation it was further clarified that in male patients’ gross total resection present in 32 patients and absent in 9 patients. Similarly, in female patients gross total resection present in 29 patients and absent in 8 patients. P value was 0.747.Conclusions: Conclusion of present study is that neuronavigation is a useful technique in for better gross total resection of intra axial brain tumors.

Molecular Classification and Management of Rare Pediatric Embryonal Brain Tumors.

Malignant embryonal brain tumors (EBTs) of childhood span a wide clinical spectrum but can share remarkably similar morphologic features. This overlap presents significant diagnostic challenges, particularly for tumor entities that are rarely encountered in clinical practice and for which diagnostic criteria were poorly defined. This review will provide an update on the evolving characterization and treatment of rare EBTs. Rapid advances in genomic tools have led to the discovery of robust molecular markers, and identification of novel tumor types and subtypes for almost all major categories of pediatric brain tumors. These developments have had significant impact on improving the diagnostic classification of the rare EBTs, particularly for tumors with newly recognized C19MC alterations, central nervous system primitive neuroectodermal tumors (CNS-PNET), and pineoblastoma (PB). These important developments in the clinical and molecular understanding of rare EBTs are paving the way for novel therapeutic strategies and improved clinical management.

Ablation dynamics during laser interstitial thermal therapy for mesiotemporal epilepsy.

IntroductionThe recent emergence of laser interstitial thermal therapy (LITT) as a frontline surgical tool in the management of brain tumors and epilepsy is a result of advances in MRI thermal imaging. A limitation to further improving LITT is the diversity of brain tissue thermoablative properties, which hinders our ability to predict LITT treatment-related effects. Utilizing the mesiotemporal lobe as a consistent anatomic model system, the goal of this study was to use intraoperative thermal damage estimate (TDE) maps to study short- and long-term effects of LITT and to identify preoperative variables that could be helpful in predicting tissue responses to thermal energy.MethodsFor 30 patients with mesiotemporal epilepsy treated with LITT at a single institution, intraoperative TDE maps and pre-, intra- and post-operative MRIs were co-registered in a common reference space using a deformable atlas. The spatial overlap of TDE maps with manually-traced immediate (post-ablation) and delayed (6-month) ablation zones was measured using the dice similarity coefficient (DSC). Then, motivated by simple heat-transfer models, ablation dynamics were quantified at amygdala and hippocampal head from TDE pixel time series fit by first order linear dynamics, permitting analysis of the thermal time constant (τ). The relationships of these measures to 16 independent variables derived from patient demographics, mesiotemporal anatomy, preoperative imaging characteristics and the surgical procedure were examined.ResultsTDE maps closely overlapped immediate ablation borders but were significantly larger than the ablation cavities seen on delayed imaging, particularly at the amygdala and hippocampal head. The TDEs more accurately predicted delayed LITT effects in patients with smaller perihippocampal CSF spaces. Analyses of ablation dynamics from intraoperative TDE videos showed variable patterns of lesion progression after laser activation. Ablations tended to be slower for targets with increased preoperative T2 MRI signal and in close proximity to large, surrounding CSF spaces. In addition, greater laser energy was required to ablate mesial versus lateral mesiotemporal structures, an effect associated with laser trajectory and target contrast-enhanced T1 MRI signal.ConclusionsPatient-specific variations in mesiotemporal anatomy and pathology may influence the thermal coagulation of these tissues. We speculate that by incorporating demographic and imaging data into predictive models we may eventually enhance the accuracy and precision with which LITT is delivered, improving outcomes and accelerating adoption of this novel tool.