Global neuro-oncology: what lies ahead for low- and middle-income countries?

Over the past few decades, the global healthcare community has achieved remarkable success in controlling many communicable diseases across various regions. However, non-communicable diseases now constitute a significant portion of disease morbidity and mortality, particularly in low- and middle-income countries (LMICs). Among these, cancer, in particular, is witnessing a notable increase in incidence in many LMICs. Among cancers, neurological tumours bear significant impact in terms of long-term disability, escalating costs of comprehensive multidisciplinary care, and often encounter resource-related and systemic delays in care leading to worse outcomes. This opinion paper discusses key concepts in developing global neuro-oncology care, with specific case examples from Pakistan to illustrate methods for improving care in these underserved regions. Additionally, it outlines strategic approaches and potential solutions to address these challenges, aiming to provide a roadmap for enhancing neuro-oncology care in LMICs.

Radiomics for precision medicine in glioblastoma.

INTRODUCTION: Being the most common primary brain tumor, glioblastoma presents as an extremely challenging malignancy to treat with dismal outcomes despite treatment. Varying molecular epidemiology of glioblastoma between patients and intra-tumoral heterogeneity explains the failure of current one-size-fits-all treatment modalities. Radiomics uses machine learning to identify salient features of the tumor on brain imaging and promises patient-specific management in glioblastoma patients. METHODS: We performed a comprehensive review of the available literature on studies investigating the role of radiomics and radiogenomics models for the diagnosis, stratification, prognostication as well as treatment planning and monitoring of glioblastoma. RESULTS: Classifiers based on a combination of various MRI sequences, genetic information and clinical data can predict non-invasive tumor diagnosis, overall survival and treatment response with reasonable accuracy. However, the use of radiomics for glioblastoma treatment remains in infancy as larger sample sizes, standardized image acquisition and data extraction techniques are needed to develop machine learning models that can be translated effectively into clinical practice. CONCLUSION: Radiomics has the potential to transform the scope of glioblastoma management through personalized medicine.

Integration of Mixed Reality Technology Into a Global Neurosurgery Bootcamp.

International bootcamps are important for providing access to advanced education and training to physicians around the world. In countries where resources are scarce, the opportunity to be exposed to advanced training and the latest technologies is limited. We set out to evaluate the educational value of integrating augmented reality (AR) into the curriculum of a global neurosurgery bootcamp. AR was integrated into this year's neurosurgical bootcamp in Hanoi, Vietnam, organized by the Foundation for International Education in Neurological Surgery (FIENS). Participants had not experienced this technology before a surgical adjunct. A study was conducted to evaluate how AR impacts the surgical approach to a cranial tumor for boot camp participants with limited neurosurgical experience. Without the use of AR, the majority of participants (66%) chose the incorrect surgical approach to a frontal tumor. However, after using AR to visualize the lesion in 3D, all participants chose the correct surgical approach. Additionally, participants were more precise when planning with AR as the distance from the skull insertion point to the tumor was significantly shorter with AR than without AR. This study demonstrated the potential of AR to improve the education and enhance the experience trainees have at international bootcamps. Importantly, it is our hope that industry involvement in these global initiatives continues to grow as it is critical for trainees in developing countries to be exposed to common as well as emerging medical technologies.

Intraoperative Augmented Reality for Complex Glioma Resection: A Case Report.

Augmented reality (AR) is an emerging technology that can display three-dimensional patient anatomy in the surgeons' field of view. The use of this technology has grown considerably for both presurgical and intraoperative guidance. A patient diagnosed with breast cancer started to experience numbness in the left hand, which progressed to weakness in the left hand and arm. An MRI was performed demonstrating a 2.9 cm X 1.8 cm lesion with extensive surrounding edema in the posterior fronto-parietal lobes. Surgery was recommended for presumed metastatic disease. Preoperatively, an AR system and Brainlab navigation were registered to the patient. AR, traditional navigation, and ultrasound were all used to localize the lesion and determine the craniotomy site and size. The tumor was removed along the direction of the lesion. Intraoperatively, we used AR to reexamine the tumor details and could appreciate that we had to redirect our surgical trajectory anteriorly and laterally in order to follow along the main axis of the tumor. In doing this, we were able to more confidently remain with the tumor, which by this time was poorly defined by 2D navigation and by direct vision. Postoperative MRI confirmed gross total removal of the tumor. The patient had an uneventful postoperative course with resolution of preoperative symptoms and the final surgical pathology was grade 4 glioblastoma. Here, we describe the valuable use of AR for the resection of a glioma. The system has a seamless registration process and provides the surgeon with a unique view of 3D anatomy overlaid onto the patient's head. This exciting technology can add tremendous value to complex cranial surgeries.

Augmented Reality Registration System for Visualization of Skull Landmarks.

BACKGROUND: Augmented reality (AR) is an emerging technology in neurosurgery with the potential to become a strategic tool in the delivery of care and education for trainees. Advances in technology have demonstrated promising use for improving visualization and spatial awareness of critical neuroanatomic structures. In this report, we employ a novel AR registration system for the visualization and targeting of skull landmarks. METHODS: A markerless AR system was used to register 3-dimensional reconstructions of suture lines onto the head via a head-mounted display. Participants were required to identify craniometric points with and without AR assistance. Targeting error was measured as the Euclidian distance between the user-defined location and the true craniometric point on the subjects' heads. RESULTS: All participants successfully registered 3-dimensional reconstructions onto the subjects' heads. Targeting accuracy was significantly improved with AR (3.59 ± 1.29 mm). Across all target points, AR increased accuracy by an average of 19.96 ± 3.80 mm. Posttest surveys revealed that participants felt the technology increased their confidence in identifying landmarks (4.6/5) and that the technology will be useful for clinical care (4.2/5). CONCLUSIONS: While several areas of improvement and innovation can further enhance the use of AR in neurosurgery, this report demonstrates the feasibility of a markerless headset-based AR system for visualizing craniometric points on the skull. As the technology continues to advance, AR is expected to play an increasingly significant role in neurosurgery, transforming how surgeries are performed and improving patient care.

Prolactinoma: Medical and Surgical Considerations.

Prolactinomas are the most common secretory tumor of the pituitary gland. Clinical symptoms may be due to prolactin oversecretion, localized mass effect, or a combination of both. Although the mainstay of prolactinoma management is medical therapy with dopamine agonists, endoscopic endonasal or transcranial surgery, radiation therapy, or a combination of these is an important treatment option in select cases. This article discusses prolactinoma phenotypes, clinical presentations, and clinically pertinent medical and surgical considerations when managing these tumors.

Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair.

Background Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity.

Tumor vascular leakiness and blood volume estimates in oligodendrogliomas using perfusion CT: an analysis of perfusion parameters helping further characterize genetic subtypes as well as differentiate from astroglial tumors.

The purpose of this study was to determine the usefulness of perfusion CT (PCT) parameters particularly blood volume and neovascular permeability estimates (permeability surface area-product, PS) in the evaluation of oligodendrogliomas (OG), correlation with genetic subtypes of OGs (with or without loss of heterozygosity/LOH on 1p/19q) as well as comparison of perfusion parameters of OGs with astroglial tumors. Pre-operative PCT done in 21 patients with OGs was retrospectively correlated with our previously published PCT data for 32 patients with astroglial neoplasms (Jain R et al., AJNR Am J Neuroradiol 29:694-700, 2008). All OGs were also analyzed for genetic subtypes of with or without LOH. PCT parameters PS and cerebral blood volume (CBV) were obtained for the entire lesion and a statistical analysis done to correlate various histopathological variants. Low grade OGs (n = 13) showed slightly lower CBV (1.42 vs. 1.72 ml/100 g; P value 0.391) and PS (0.56 vs. 0.95 ml/100 g/min; P value 0.099) as compared to high grade OGs (n = 8), though not statistically significant. LOH positive OGs (n = 13) showed higher mean CBV (1.59 vs. 1.45; P value 0.712) and slightly lower PS (0.68 vs. 0.75; P value 0.718) as compared to LOH negative OGs (n = 8), although not statistically significant. Low grade OGs (n = 13) showed higher mean CBV 1.42 ml/100 g as compared to low grade astroglial tumors (n = 8) 0.95 ml/100 g (P value = 0.08), however no statistically significant difference was noted for PS (0.56 vs. 0.52 ml/100 g/min, P value 0.695). Statistically significant differences were observed in CBV and PS values of high grade OGs and high grade astroglial tumors with the high grade glial tumors showing higher mean CBV (2.79 vs. 1.72; P value 0.03) as well as higher PS (2.37 vs. 0.95; P value < 0.01), however this difference was not significant if only comparing grade III OGs with grade III astroglial tumors. PCT perfusion parameters including PS values do not help grade OGs despite showing a trend for higher CBV and PS in higher grade OGs. Similarly LOH positive OGs also showed slightly higher CBV, but again failed to reach any statistically significant level. Low grade OGs showed slightly higher CBV as compared to low grade astroglial tumors, whereas higher grade OGs showed significantly lower PS values as compared to higher grade astroglial tumors despite showing high CBV.

Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs.

BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P < .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns.

Treatment induced necrosis versus recurrent/progressing brain tumor: going beyond the boundaries of conventional morphologic imaging.

Brain tumor patients undergo various combinations therapies, leading to very complex and confusing imaging appearances on follow up MR imaging and hence, differentiating recurrent or progressing tumors from treatment induced necrosis or effects has always been a challenge in neuro-oncologic imaging. This particular topic has become more relevant these days because of the advent of newer anti-angiogenic and anti-neoplastic chemotherapeutic agents as well as use of salvage radiation therapy. Various clinically available functional imaging modalities can provide additional physiologic and metabolic information about the tumors which could be useful in identifying viable tumor from treatment induced necrosis and hence, can guide treatment planning. In this review we will discuss various functional neuro-imaging modalities, their advantages and limitations and also their utility in treatment planning.

Can permeability measurements add to blood volume measurements in differentiating tumefactive demyelinating lesions from high grade gliomas using perfusion CT?

Tumefactive demyelinating lesions (TDLs) can mimic a neoplasm on conventional imaging and may necessitate biopsy for diagnosis. The purpose of this study was to differentiate TDLs from high grade gliomas based on physiologic (permeability) and hemodynamic (blood volume) parameters using perfusion CT. Five patients who presented with tumefactive enhancing lesions on initial MRI that mimicked a neoplasm underwent perfusion CT. We compared the perfusion CT parameters of these patients with those of 24 patients with high grade gliomas. TDLs showed lower permeability surface area product (PS) (0.8 +/- 0.2 vs 2.4 +/- 1.4 ml/100 g/min, P-value 0.014) and lower cerebral blood volume (CBV) (1.0 +/- 0.2 vs 2.8 +/- 1.2 ml/100 g, P-value 0.006) as compared to high grade gliomas. TDLs show lower PS and CBV as compared to high grade gliomas, to which they can mimic on conventional MR imaging, due to lack of neoangiogenesis and vascular endothelial proliferation and hence perfusion CT can be used to differentiate the two entities.

Clinical, dosimetric, and radiographic correlation of radiation injury involving the brainstem and the medial temporal lobes following stereotactic radiotherapy for neoplasms of central skull base.

Stereotactic Radiotherapy (SRT) is more commonly used for skull base tumors in conjunction with the technical development of radiation intensity modulation. Purpose of this study is to correlate clinical and radiographic characteristics of delayed radiation injury (RI) occurring around central skull base following SRT with SRT dosimetric data. Total of six patients were identified to have developed RI in the vicinity of SRT target volume out of 141 patients who received SRT in he center or near-center of the skull base. The images and medical records were retrospectively reviewed. The analysis was performed for RI location, time of development, imaging and clinical characteristics and evolution of RI and correlated with SRT dosimetric analysis using image fusion with follow-up MRI scans. Mean follow-up time was 24 +/- 9 months. During the follow-up period, twelve sites of RI were found in 6 patients. They were clinically symptomatic in 4/6 patients (66.6%) at median 12.5 months after SRT. Mean time interval between SRT and detection of RI was 9 +/- 3, 18.5 +/- 5, and 13.5 months for brainstem, temporal lobe, and cerebellum/labyrinth lesions, respectively. All RI lesions were included in the region of high SRT doses. After steroid and symptomatic treatment, 50% of RI lesions showed complete response, and 40% showed partial response. RI can occur around the skull base because of irregular shape of target tumor, its close proximity to normal brain parenchyma, and inhomogeneity of dose distribution. Brainstem lesions occurred earlier than temporal lobe RI. The majority of the RI lesions, not mixed with the tumor in this study, showed radiographic and clinical improvement with steroid and symptomatic treatments.

Cranial angiomatoid fibrous histiocytoma: A case report and review of literature.

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare low-grade soft-tissue tumor that typically arises from the deep dermal and subcutaneous tissue of the extremities in children and young adults. Intracranial AFH is exceedingly rare, and only four cases of primary AFH tumors have been reported to date. CASE DESCRIPTION: A 43-year-old male presented to our hospital with headaches, vision changes, and a known brain tumor suspected to be an atypical meningioma. After undergoing craniotomy for resection of the mass, the immunomorphologic features of the resected tumor showed typical features of AFH with ESWR1 (exon7) - ATF1 (exon 5) fusion. CONCLUSION: AFH is a difficult tumor to diagnose with imaging and histologic studies. Thus, further knowledge is necessary - particularly of intracranial cases - to aid clinicians in its diagnosis and management.

Traumatic Brain Injury in Myanmar: Preliminary Results and Development of an Adjunct Electronic Medical Record.

BACKGROUND: The treatment of traumatic brain injury (TBI) in Myanmar is a major health issue. Comprehensive appreciation of the pathology is limited given the lack of granular metadata available. In this proof-of-concept study, we analyzed demographic data on TBI generated from a novel, prospective, online database in a lower-middle income country. METHODS: Neurosurgery residents were given an electronic tablet for data entry into an online database. Metadata-driven data capture was carried out prospectively by trained residents, and the information was reviewed weekly by the supervising team in the United States. RESULTS: Complete data were available on 242/253 (96%) patients. Age at admission was 37 years (range 16-85), and length of stay was 3.53 days (1-21). Etiologies included motorcycle accidents, falls, assaults, pedestrian vehicular injuries, and industrial accidents. Dispositions were primarily to home (211). Average Glasgow Coma Scale score at admission was 12.97. There was a 68% mortality rate of patients directly admitted to the North Okkalappa General and Teaching Hospital with a Glasgow Coma Scale score <8 versus 75% for patients transferred in from other facilities. Surgery was performed on 30 patients (12.4%). CONCLUSIONS: Despite a lack of formal training in electronic medical records or research, the resident team was able to capture the majority of admissions with granular-level data. This helped shed light on the etiology and severity of TBI in Myanmar. As a result, more effective transport systems and access to trauma care must be achieved. Accessible regional trauma centers with investment in intensive care units, operative care, anesthesia, and imaging resources are necessary.

Beta-2 transferrin is detectable for 14 days whether refrigerated or stored at room temperature.

BACKGROUND: The effect of time and temperature on beta-2 transferrin stability in cerebrospinal fluid (CSF) is not well established. After collecting nasal CSF for testing, beta-2 transferrin has been found to be stable and detectable for 1 week, whether being refrigerated or stored at room temperature. The purpose of this study was to determine if beta-2 transferrin remained detectable longer than 1 week and whether refrigeration improved its detectability. METHODS: In patients undergoing therapeutic CSF diversion, 2-mL CSF samples were collected from 18 patients. The samples were divided and stored either at room temperature, or at 4°C, and tested for beta-2 transferrin at 7 and 14 days. CSF was collected from external ventricular drains (EVDs) (n = 15), lumbar drains (n = 2), and subdural drains (n = 1). RESULTS: Of the 18 CSF samples originally testing positive for beta-2 transferrin, none turned negative at 7 or 14 days, in both the refrigerated and room temperature groups (95% confidence interval [CI], 0% to 18.5%). CONCLUSION: Beta-2 transferrin remained detectable for 14 days in all CSF samples, regardless of being stored at 4°C or room temperature.

Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases.

OBJECT: The aim of this study was to evaluate the effectiveness of brachytherapy using the GliaSite Radiation Therapy System in patients with a newly diagnosed resected single brain metastasis. The primary end point of the study was local tumor control. The secondary end points included patient survival, distant brain recurrence, quality of life, and treatment toxicity. METHODS: The authors conducted a prospective multiinstitutional phase II study of GliaSite brachytherapy prescribed at a 60-Gy dose administered to a 1-cm depth after resection of a single brain metastasis. No whole-brain radiation therapy was given. Patients were assessed at 1 and 3 months after brachytherapy and every 3 months thereafter for up to 2 years. Seventy-one patients were enrolled at 13 centers. A GliaSite balloon catheter was implanted in 62 patients. Fifty-four patients received brachytherapy. The median patient age was 60 years. The most common tumor (54%) was non-small cell lung cancer. Fifty-seven percent of patients had brain metastasis only, whereas 43% had extracranial metastasis. The median final administered dose was 60 Gy. The magnetic resonance imaging--determined local control rate, based on several different methods, was 82 to 87%. Both the median patient survival time and the median duration of functional independence were 40 weeks. Among the 35 patients who died, the cause of death was neurological in 11%. Thirteen patients underwent reoperation for suspected tumor recurrence or radiation necrosis, and histological diagnoses included radiation necrosis without tumor (nine patients), radiation necrosis mixed with tumor (two patients), and tumor only (two patients). Extracranial metastasis, tumor size, and radiation necrosis were significant factors affecting patient survival. CONCLUSIONS: In patients with a resected single brain metastasis, GliaSite brachytherapy leads to a local control rate, median patient survival time, and duration of functional independence similar to those achieved with resection plus whole-brain radiation therapy.

Preoperative external tissue expansion for complex cranial reconstructions.

OBJECTIVE Reconstruction of large solitary cranial defects after multiple craniotomies is challenging because scalp contraction generally requires more than simple subcutaneous undermining to ensure effective and cosmetically appealing closure. In plastic and reconstructive surgery, soft tissue expansion is considered the gold standard for reconstructing scalp defects; however, these techniques are not well known nor are they routinely practiced among neurosurgeons. The authors here describe a simple external tissue expansion technique that is associated with low morbidity and results in high cosmetic satisfaction among patients. METHODS The authors reviewed the medical records of patients with large cranial defects (> 5 cm) following multiple complicated craniotomies who had undergone reconstructive cranioplasty with preoperative tissue expansion using the DermaClose RC device. In addition to gathering data on patient age, sex, primary pathology, number of craniotomies and/or craniectomies, history of radiation therapy, and duration of external scalp tissue expansion, the authors screened patient charts for cerebrospinal fluid (CSF) leak, meningitis, intracranial abscess formation, dermatitis, and patient satisfaction rates. RESULTS The 6 identified patients (5 female, 1 male) had an age range from 36 to 70 years. All patients had complicating factors such as recalcitrant scalp infections after multiple craniotomies or cranial radiation, which led to secondary scalp tissue scarring and retraction. All patients were deemed to be potential candidates for rotational flaps with or without skin grafts. All patients underwent the same preoperative tissue expansion followed by standard cranial bone reconstruction. None of the patients developed CSF leak, meningitis, intracranial abscess, dermatitis, or permanent cosmetic defects. None of the patients required a reoperation. Mean follow-up was 117 days. CONCLUSIONS Preoperative scalp tissue expansion with the DermaClose RC device allows for simple and reliable completion of complicated cranial reconstruction with low morbidity rates and high cosmetic satisfaction among patients.

Contralateral hearing loss after vestibular schwannoma excision: a rare complication of neurotologic surgery.

We report a rare case of contralateral hearing loss after vestibular schwannoma excision in a 48-year-old man who underwent surgery via a suboccipital approach for removal of a nearly 2-cm lesion involving the right cerebellopontine angle. Postoperatively, the patient awoke with bilateral deafness, confirmed by both audiometry and spontaneous otoacoustic emissions. The patient was treated aggressively with high-dose intravenous steroids, vitamins E and C, and oxygen. Over the next several months he had gradual recovery of most of the hearing in his left (unoperated) ear. Contralateral hearing loss may develop after vestibular schwannoma excision; multiple pathophysiologic mechanisms for this occurrence have been proposed.

Associations among magnetic resonance spectroscopy, apparent diffusion coefficients, and image-guided histopathology with special attention to radiation necrosis.

OBJECTIVE: In patients with malignant glioma previously treated with surgery, radiation, and chemotherapy, clinical and radiographic signs of recurrent disease often require differentiation between radiation necrosis and recurrent tumor. Published work suggests that although magnetic resonance spectroscopy (MRS) can reliably differentiate pure tumor, pure necrosis, and spectroscopically normal tissues, it may not be particularly helpful because most patients have mixed histological findings comprised of necrosis and tumor. To improve our clinical ability to discriminate among these histological entities, we have analyzed MRS in conjunction with apparent diffusion coefficient (ADC) sequences derived from magnetic resonance imaging. METHODS: In 18 patients, spectroscopic and diffusion-weighted images were obtained before surgery for suspected recurrent neoplastic disease. Spectral data for pure tumor, pure necrosis, and mixed tumor and necrosis were derived from 65 spectroscopic observations in patients with previously treated gliomas (n = 16) and metastatic tumors (n = 2). Spectral data for choline (Cho), N-acetylaspartate (NAA), creatine (Cr), and lipid-lactate were analyzed separately and in conjunction with ADCs in all patients (15 observations of pure tumor, 33 observations of pure necrosis, and 13 observations of mixed tumor and necrosis). Histological specimens were obtained stereotactically at the time of surgery (<48 h after image acquisition) for recurrent disease and digitally co-registered with MRS data. RESULTS: ADC values for pure tumor, pure necrosis, and mixed tumor and necrosis were 1.30, 1.60, and 1.42, respectively. Cho/NAA less than 0.20, NAA/normal Cr greater than 1.56, and NAA/Cho greater than 1.32 increase the odds that a tissue biopsy will be pure necrosis versus mixed tumor and necrosis. Although various values of all MRS ratios analyzed may provide positive correlations for histopathological differentiation of tissue between that of pure tumor and that of pure necrosis, the addition of ADC values to only NAA/Cho and NAA/normal Cr increases the odds of correct differentiation between pure tumor and pure necrosis. The addition of ADC values does not provide additional information beyond that of MRS in distinguishing specimens of mixed tumor and necrosis from either pure tumor or pure necrosis. CONCLUSION: It has been demonstrated that MRS ratio analysis may allow for the clinical discrimination between specimens of pure tumor and pure necrosis, and the addition of ADC data into this analysis may enhance this specific differentiation. However, although a trend toward correlation between ADC values and the various histopathological features was noted, the direct addition of ADC data does not seem to allow further discrimination, beyond that provided by MRS, among specimens of mixed tumor and necrosis and either pure tumor or pure necrosis.