The challenges and opportunities of global neurosurgery in East Africa: the Neurosurgery Education and Development model.

OBJECTIVE: The objective of this study was to describe the experience of a volunteering neurosurgeon during an 18-week stay at the Neurosurgery Education and Development (NED) Institute and to report the general situation regarding the development of neurosurgery in Zanzibar, identifying the challenges and opportunities and explaining the NED Foundation's model for safe practice and sustainability. METHODS: The NED Foundation deployed the volunteer neurosurgeon coordinator (NC) for an 18-week stay at the NED Institute at the Mnazi Mmoja Hospital, Stonetown, Zanzibar. The main roles of the NC were as follows: management of patients, reinforcement of weekly academic activities, coordination of international surgical camps, and identification of opportunities for improvement. The improvement opportunities were categorized as clinical, administrative, and sociocultural and were based on observations made by the NC as well as on interviews with local doctors, administrators, and government officials. RESULTS: During the 18-week period, the NC visited 460 patients and performed 85 surgical procedures. Four surgical camps were coordinated on-site. Academic activities were conducted weekly. The most significant challenges encountered were an intense workload, deficient infrastructure, lack of self-confidence among local physicians, deficiencies in technical support and repairs of broken equipment, and lack of guidelines. Through a series of interviews, the sociocultural factors influencing the NED Foundation's intervention were determined. Factors identified for success were the activity of neurosurgical societies in East Africa; structured pan-African neurosurgical training; the support of the Foundation for International Education in Neurological Surgery (FIENS) and the College of Surgeons of East, Central and Southern Africa (COSECSA); motivated personnel; and the Revolutionary Government of Zanzibar's willingness to collaborate with the NED Foundation. CONCLUSIONS: International collaboration programs should balance local challenges and opportunities in order to effectively promote the development of neurosurgery in East Africa. Support and endorsement should be sought to harness shared resources and experience. Determining the caregiving and educational objectives within the logistic, administrative, social, and cultural framework of the target hospital is paramount to success.

Dural arteriovenous fistula at the foramen magnum: Report of a case and clinical-anatomical review.

Arterial supply and venous drainage at the foramen magnum is variable. Two main forms of clinical presentation, intracranial and spinal, can be differentiated when a dural arteriovenous fistula (DAVF) is found at this level. We describe a case of a 68-year-old patient with a progressive paraparesis, diagnosed of dural arteriovenous fistula located at the posterior lip of foramen magnum. We review, in this setting, the vascular radiological anatomy of those fistulas and its important correlation with neurologic clinical symptoms.

Clinical Capacity Building Through Partnerships: Boots on the Ground in Global Neurosurgery.

Global neurosurgery seeks to provide quality neurosurgical health care worldwide and faces challenges because of historical, socioeconomic, and political factors. To address the shortfall of essential neurosurgical procedures worldwide, dyads between established neurosurgical and developing centers have been established. Concerns have been raised about their effectiveness and ability to sustain capacity development. Successful partnerships involve multiple stakeholders, extended timelines, and twinning programs. This article outlines current initiatives and challenges within the neurosurgical community. This narrative review aims to provide a practical tool for colleagues embarking on clinical partnerships, the Engagements and assets, Capacity, Operative autonomy, Sustainability, and scalability (ECOSystem) of care. To create the ECOSystem of care in global neurosurgery, the authors had multiple online discussions regarding important points in the practical tool. All developed tiers were expanded based on logistics, clinical, and educational aspects. An online search was performed from August to November 2023 to highlight global neurosurgery partnerships and link them to tiers of the ECOSystem. The ECOSystem of care involves 5 tiers: Tiers 0 (foundation), 1 (essential), 2 (complexity), 3 (autonomy), and 4 (final). A nonexhaustive list of 16 neurosurgical partnerships was created and serves as a reference for using the ECOSystem. Personal experiences from the authors through their partnerships were also captured. We propose a tiered approach for capacity building that provides structured guidance for establishing neurosurgical partnerships with the ECOSystem of care. Clinical partnerships in global neurosurgery aim to build autonomy, enabling independent provision of quality healthcare services.

[Recommendations on the use of 5-amino-levulinic acid in surgery of malignant gliomas. Consensus document. The Neuro-oncology Working Group of the Spanish Neurosurgical Society (SENEC)]. / Recomendaciones sobre el uso de ácido 5-aminolevulínico en la cirugía de los gliomas malignos. Documento de consenso.

Among the prognostic factors when it comes to patients with high-grade gliomas, we find the radicality of the surgery performed. The limitations of this factor are caused by either the extension of the tumour or its location in an eloquent area. To achieve this goal, in the last few years we have developed several methods that allow us to maximise tumour resection, while always trying to cause the least possible co-morbidity. One of these methods includes the use of 5-amino-levulinic acid (5-ALA) and the development of fluorescence guided surgery. However, optimal performance requires knowledge of the product employed, the mode of administration and precautions to consider. Members of the neuro-oncology work group of the Spanish Neurosurgical Society (SENEC) have prepared this guideline or consensus document for anyone who wishes to become familiar with the use of 5-ALA fluorescence-guided surgery in the management of high-grade gliomas. For those who already utilise this technique, this document can be useful for consultation purposes.

[Mini-open approaches in anterior lumbar spine surgery]. / Abordajes anteriores mini-open en el raquis toracolumbar.

INTRODUCTION: The anterior spine approach known as «mini-open¼ was introduced a few years ago for the surgical treatment of spine diseases. This approach allows the anterior, body and intervertebral disc structures to be exposed, as well as the anterior compression of the dural sac and the reconstruction and/or stabilisation of the levels of interest with an appropriate system. In the present article we present our experience in mini-open anterior spine surgery (MOASS) approach in the treatment of lumbar spine diseases. MATERIAL AND METHODS: We performed 74 anterior spine approaches using open surgery between the period January 2004 and July 2011. In 38 cases we used the MOASS technique at different levels: thoracic, lumbar, and infraumbilical extraperitoneal. RESULTS: There were no surgical or post-operative deaths, or further neurological deficits arising from the surgical procedure in any of the techniques (classic versus MOASS). The few complications were corrected with the appropriate treatment. CONCLUSIONS: Using the MOASS technique we have performed corrective surgery on spine injuries that could affect the thoracic spinal column, with similar results to those obtained using the classic approach and with obvious advantages.

Whole-genomic survey of oligodendroglial tumors: correlation between allelic imbalances and gene expression profiles.

Malignant gliomas are the most common subtype of primary central nervous system (CNS) tumors. Their pathological classification, however, remains subjective, stimulating researchers to actively seek objective molecular markers to discover alternative and more reproducible tools for improved subtypification. Herein, we present a global survey of genomic alterations in oligodendroglial tumors (OT). Genetic and epigenetic alterations identified in this study are correlated with OT molecular groups we have recently reported: a neurogenic group composed of tumors with loss of heterozygosity (LOH) at 1p-19q, IDH1 mutations, and MGMT promoter methylation, showing good prognosis; an intermediate group, presenting TP53 mutations or LOH at 17p, IDH1 mutations, and GSTP1 promoter methylation; and a proliferative group, presenting major genetic alterations (LOH at 10q, EGFR amplification, and CDKN2A/ARF deletion) and poor prognosis. These results allowed us to refine our molecular characterization associated with prognosis, referring exclusively to oligodendroglial tumors.

Loss of heterozygosity at 1p-19q induces a global change in oligodendroglial tumor gene expression.

Oligodendroglial tumors presenting loss of heterozygosity (LOH) at 1p and 19q have been shown to be sensitive to chemotherapy, thus making 1p-19q status testing a key aspect in oligodendroglioma diagnosis and prognosis. Twenty-nine tumor samples (19 oligodendrogliomas, 10 oligoastrocytomas) were analyzed in order to obtain a molecular profile identifying those bearing 1p-19q LOH. Other genomic anomalies usually present in gliomas, such as EGFR amplification, CDKN2A/ARF deletion, 10q LOH and TP53 mutation, were also studied. Tumors with 1p-19q LOH overexpressed genes related to neurogenesis. Genes linked to immune response, proliferation and inflammation were overexpressed in the group with intact 1p-19q; this group could in turn be further divided in two subgroups: one overexpressing genes involved in immune response and inflammation that did not show major genetic aberrations other than the TP53 mutation and EGFR trisomy in a few cases, and another overexpressing genes related to immune response and proliferation that had a predominance of samples carrying several anomalies and presenting worse outcomes. This molecular signature was validated by analyzing a set of ten tumor samples (three oligodendrogliomas, seven oligoastrocytomas); all ten samples were correctly assigned. LOH at 1p-19q results in haploinsufficiency and copy number reduction of several genes, including NOTCH 2; this phenomenon produces a global change in gene expression inducing a pro-neural status that results in restrictions to cell migration and proliferation. Tumors without LOH at 1p-19q exhibit the opposite characteristics, explaining their more aggressive behavior.

Experience in the Early Surgical Management of Myelomeningocele in Zanzibar.

BACKGROUND: Neural tube defects are a large health burden for East African countries. Health strategies in the prevention of this disease include nutritional prophylaxis, prenatal diagnosis, and availability of early neonatal neurosurgery. The main objective of this study is to describe our experience in the early surgical management of neural tube defects in the Zanzibar archipelago. METHODS: From December 2016 to December 2017, we prospectively collected data on all patients admitted with the diagnosis of myelomeningocele. We collected variables regarding demographics, maternal health, preoperative imaging, surgical procedures, and complications at follow-up. RESULTS: We collected data on 19 patients. Mean age was 9.8 ± 18.7 days. Of these patients, 52.6% were male and 47.3% were female; 47.3% patients were from Unguja, 42.0% from Pemba, and 5.2% from mainland Tanzania; 68.4% of all mothers were found to have undergone prenatal ultrasonography and 89.5% of all patients received surgery. Surgical wound infection was present in 29.4% of all surgical patients and 52.9% developed secondary hydrocephalus. CONCLUSIONS: Neural tube defects are a prevailing condition in East Africa. We believe that more health initiatives should address its prevention, mainly through maternal nutrition. On the basis of our findings, we consider early neonatal neurosurgery as the most important factor in reducing immediate morbidity and mortality.

Postoperative CSF leakages after transsphenoidal surgery for pituitary adenomas: Analysis of a series of 302 surgical procedures. / Fístulas posquirúrgicas de líquido cefalorraquídeo tras cirugía transesfenoidal de adenomas hipofisarios: análisis de una serie de 302 intervenciones.

INTRODUCTION: Transsphenoidal surgical removal is the preferred treatment of most pituitary adenomas. Postoperative cerebrospinal fluid (CSF) leakage is the leading cause of morbidity after this procedure, with an incidence rate that varies from 0,5-15% in the main published series. OBJECTIVES: The primary objective of this study was to establish the incidence of postoperative CSF leakage in a sample of surgeries performed at the University Hospital of La Ribera by the same surgical team. The secondary objectives were to: ascertain the distinctive features between patients with and without postoperative CSF leakage, identify risk factors for their development, evaluate the relationship between the surgical technique for closing the sella turcica and the onset of postoperative CSF leakage and evaluate different treatment regimens for this complication. METHODS: The data of 302 consecutive transsphenoidal surgical procedures for pituitary adenoma removal which were performed between 1999 and 2017 were retrospectively reviewed. RESULTS AND CONCLUSIONS: The incidence of postoperative CSF leakage in our series was 2,3% (in accordance with similar published studies). It was possible to correlate intraoperative CSF leakage with two variables: pituitary macroadenoma and tumors with suprasellar extension (P<.005). This correlation did not exist for postoperative CSF leakage. We found a statistically significant correlation between intraoperative and postoperative CSF leakage (P<.005). Due to the low incidence of postoperative CSF leakage in our series, it was not possible to identify risk factors for its development.

Practical Challenges and Perspectives for the Development of Neurosurgery in a Peripheral East African Hospital During a One-Volunteer Midterm Mission.

BACKGROUND: Several strategies have been proposed for developing and spreading surgical specialties in Sub-Saharan East Africa. Regarding neurosurgery, improvements are coming from the cooperation between Western and African institutes by means of the World Federation of Neurological Surgeons and independent organizations but, far from big cities and more equipped hospitals, shortcomings in the delivery of services persist. METHODS: Through the application of 1 formally trained neurosurgeon volunteer, the Foundation for International Education in Neurological Surgery and Neurocirugía, Educación y Desarrollo coordinated a 2-month neurosurgical project at Mathari Consolata Hospital in Nyeri (Kenya), designed to analyze critical points and to find suggestions for initiating and developing a neurosurgical service, providing in the meantime clinical and surgical care for patients. RESULTS: During the mission, general and local issues limiting the neurosurgical activities at the hospital were studied. They were discussed with the hospital board and the project supervisors, thereby ensuring short-term and medium-term solutions and possible future cooperation with the hospital. The volunteer also carried out clinics and surgery for neuro cases and neurosurgical training for nurses and doctors. CONCLUSIONS: The model proposed should be considered a preliminary and immersive survey to evaluate the eligibility of a decentralized East African hospital to interface with neurosurgical activities, through the support of experienced local institutes and Western organizations. Host hospitals would also have the chance to enhance clinical services currently lacking and to train its personnel at low cost. The program may represent a rewarding personal and professional opportunity for young trained neurosurgeons, which also addresses the contemporary shortage of local specialists.

Treating Pediatric Hydrocephalus at the Neurosurgery Education and Development Institute: The Reality in the Zanzibar Archipelago, Tanzania.

BACKGROUND: Pediatric hydrocephalus is a health burden for East African countries, with an estimated incidence of 6000 new cases per year. The objective of this study is to describe the epidemiology and surgical outcomes of patients treated for pediatric hydrocephalus in the single neurosurgical center of Zanzibar. METHODS: From December 2016 to December 2017, we prospectively collected data on all patients admitted with the diagnosis of hydrocephalus. Information was gathered regarding demographics, maternal health, preoperative imaging, surgical procedures, and postsurgical complications. RESULTS: We collected data on 63 patients. Average age was 203 days, and gender was 49.2% female and 50.8% male. All mothers of patients attended an antenatal clinic for routine screening during pregnancy. Folic acid prophylaxis was used by 9.5% of the mothers during pregnancy. At the first visit, 46.0% of patients presented with signs of infection, 20.6% with congenital abnormalities, and 20.6% with seizures. Regarding etiology of hydrocephalus, 22.2% of all cases were uncertain; 20.6% were associated with neural tube defects; 39.7% were postinfectious hydrocephalus; 3.2% were aqueduct stenosis; 4.8% were associated with brain tumor; and 9.6% were malformative. We performed 7 endoscopic third ventriculostomies and placed 40 ventriculoperitoneal shunts. The complication rate at follow-up was 12.5%. CONCLUSIONS: It seems that hydrocephalus in Zanzibar has similar causes, progression, and complication rates to previous reports from other African hospitals. Further studies of postinfectious hydrocephalus need to be conducted because recent findings suggest that it is a potentially preventable cause of the disease.

Neurosurgery in East Africa: Innovations.

In the last 10 years, considerable work has been done to promote and improve neurosurgical care in East Africa with the development of national training programs, expansion of hospitals and creation of new institutions, and the foundation of epidemiologic and cost-effectiveness research. Many of the results have been accomplished through collaboration with partners from abroad. This article is the third in a series of articles that seek to provide readers with an understanding of the development of neurosurgery in East Africa (Foundations), the challenges that arise in providing neurosurgical care in developing countries (Challenges), and an overview of traditional and novel approaches to overcoming these challenges to improve healthcare in the region (Innovations). In this article, we describe the ongoing programs active in East Africa and their current priorities, and we outline lessons learned and what is required to create self-sustained neurosurgical service.

CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas.

PURPOSE: The DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents, and its loss in cancer cells is associated with hypermethylation of the MGMT CpG island. Thus, methylation of MGMT has been correlated with the clinical response to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in primary gliomas. Here, we investigate whether the presence of MGMT methylation in gliomas is also a good predictor of response to another emergent alkylating agent, temozolomide. EXPERIMENTAL DESIGN: Using a methylation-specific PCR approach, we assessed the methylation status of the CpG island of MGMT in 92 glioma patients who received temozolomide as first-line chemotherapy or as treatment for relapses. RESULTS: Methylation of the MGMT promoter positively correlated with the clinical response in the glioma patients receiving temozolomide as first-line chemotherapy (n = 40). Eight of 12 patients with MGMT-methylated tumors (66.7%) had a partial or complete response, compared with 7 of 28 patients with unmethylated tumors (25.0%; P = 0.030). We also found a positive association between MGMT methylation and clinical response in those patients receiving BCNU (n = 35, P = 0.041) or procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (n = 17, P = 0.043) as first-line chemotherapy. Overall, if we analyze the clinical response of all of the first-line chemotherapy treatments with temozolomide, BCNU, and procarbazine/1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea as a group in relation to the MGMT methylation status, MGMT hypermethylation was strongly associated with the presence of partial or complete clinical response (P < 0.001). Finally, the MGMT methylation status determined in the initial glioma tumor did not correlate with the clinical response to temozolomide when this drug was administered as treatment for relapses (P = 0.729). CONCLUSIONS: MGMT methylation predicts the clinical response of primary gliomas to first-line chemotherapy with the alkylating agent temozolomide. These results may open up possibilities for more customized treatments of human brain tumors.

Neurosurgery Education and Development program to treat hydrocephalus and to develop neurosurgery in Africa using mobile neuroendoscopic training.

OBJECT A shortage of neurosurgeons and a lack of knowledge of neuroendoscopic management of hydrocephalus limits modern care in sub-Saharan Africa. Hence, a mobile teaching project for endoscopic third ventriculostomy (ETV) procedures and a subsequent program to develop neurosurgery as a permanent specialty in Kenya and Zanzibar were created and sponsored by the Neurosurgery Education and Development (NED) Foundation and the Foundation for International Education in Neurological Surgery. The objective of this work was to evaluate the results of surgical training and medical care in both projects from 2006 to 2013. METHODS Two portable neuroendoscopy systems were purchased and a total of 38 ETV workshops were organized in 21 hospitals in 7 different countries. Additionally, 49 medical expeditions were dispatched to the Coast General Hospital in Mombasa, Kenya, and to the Mnazi Moja Hospital in Zanzibar. RESULTS From the first project, a total of 376 infants with hydrocephalus received surgery. Six-month follow-up was achieved in 22%. In those who received follow-up, ETV efficacy was 51%. The best success rates were achieved with patients 1 year of age or older with aqueductal stenosis (73%). The main causes of hydrocephalus were infection (56%) and spina bifida (23%). The mobile education program interacted with 72 local surgeons and 122 nurses who were trained in ETV procedures. The second project involved 49 volunteer neurosurgeons who performed a total of 360 nonhydrocephalus neurosurgical operations since 2009. Furthermore, an agreement with the local government was signed to create the Mnazi Mmoja NED Institute in Zanzibar. CONCLUSIONS Mobile endoscopic treatment of hydrocephalus in East Africa results in reasonable success rates and has also led to major developments in medicine, particularly in the development of neurosurgery specialty care sites.

Fluorescence-guided surgery and biopsy in gliomas with an exoscope system.

BACKGROUND: The introduction of fluorescence-guided resection allows a better identification of tumor tissue and its more radical resection. We describe our experience with a modified exoscope to detect 5 ALA-induced fluorescence in neuronavigation-guided brain surgery or biopsy of malignant brain tumors. METHODS: Thirty-eight patients with a suspected preoperative diagnosis of high-grade astrocytoma were included. We used a neuronavigation device and a high-definition exoscope system with a built-in filter to detect 5-ALA fluorescence in all cases. Thirty patients underwent craniotomy with tumor resection and 8 underwent frameless stereotactic brain biopsy. RESULTS: Histopathological diagnosis confirmed the presence of high-grade gliomas in 34 patients. Total resection was achieved in 23 cases and subtotal in 7. No relevant complications related to the administration of 5-ALA were detected. CONCLUSIONS: The use of the exoscope in 5-ALA fluorescence-guided tumor surgery has twofold implications: during brain tumor surgery it can be considered a valuable tool to achieve a more radical resection of the lesion, and when applied to a biopsy of a suspected brain high-grade glioma, it decreases the possibility of a negative biopsy.

Mobile endoscopy: a treatment and training model for childhood hydrocephalus.

BACKGROUND: Hydrocephalus, largely a disease of poverty in many developing regions such as Sub-Saharan Africa, becomes even more challenging to treat because of lack of trained neurosurgical personnel, inadequately equipped public health care facilities, meager resource allocation, high rates of neonatal infection, difficulty of access to tertiary care hospitals able to treat hydrocephalus, and high complication rates in patients who are able to access and receive shunting procedures. Furthermore, conventional methods of training of neurosurgeons and nursing staff to become proficient in neuroendoscopic procedures involve a lengthy period of training, often at specialized centers in Western or local Western-style institutions. METHODS: The novel approach promoted by volunteer neurosurgical teams from Neurosurgery Education Development Foundation is described, and its potential role in successfully providing neuroendoscopic ventriculostomy at hospitals in regional sites away from main referral tertiary hospitals is outlined. The impact on the training of local neurosurgical specialists and residents in training as well as nursing staff is highlighted. RESULTS: With the use of a single portable neuroendoscopy system and a versatile free-hand, single-operator neuroendoscope, this outreach, mobile, and readily portable model has been successfully used to perform more than 250 procedures in 21 different hospital sites around seven different countries in two continents. The local courses have imparted hands-on training to 62 neurosurgeons and trainee residents and a further 110 operating room nurses at these 21 institutions. CONCLUSIONS: Neuroendoscopy is not only a priority surgical tool for East Africa. It offers a medical philosophy as an application that serves as an art and a science dedicated to the development of a complex surgical specialty: neurosurgery.

Impact of mobile endoscopy on neurosurgical development in East Africa.

Hydrocephalus, a disease frequently associated with poverty, becomes even more challenging to treat in developing regions because of lack of neurosurgical manpower, inadequately equipped public health care facilities, meager resource allocations, high rates of neonatal infection, difficulty of accessibility to hospitals able to treat hydrocephalus, and high complication rates in patients who are able to access and receive shunting procedures. Definitive treatment of hydrocephalus that avoids shunting procedures and long-term shunt dependence is a safer option. In environments such as Sub-Saharan Africa (and, indeed, in other similar resource-challenged regions), neuroendoscopic ventriculostomy (NEV), in appropriately selected patients can overcome the problems associated with shunting, including long-term shunt dependence. A novel approach promoted by volunteer neurosurgical teams from the Neurosurgery Education Development (NED) Foundation is described, and its important role in successfully providing NEV at hospitals in regional sites away from main tertiary referral hospitals is outlined. Using a single portable neuroendoscopy equipment system and a versatile free-hand, single operator neuroendoscope, an easily mobile outreach model has been successfully used to perform 187 procedures in 19 hospital sites around six countries and on two continents. Neuroendoscopy is not just a priority surgical tool for East Africa; it represents a best practices philosophy of what is possible within a highly sophisticated surgical speciality like neurosurgery in developing countries. It offers an opportunity to highlight the importance of tertiary care specialties like neurosurgery in this region, to develop closer relationships between African neurosurgeons and to convince medical students, general residents, and nurses that "world-class neurosurgery" can be possible in a developing region.

Determination of metabolite concentrations in human brain tumour biopsy samples using HR-MAS and ERETIC measurements.

Accurate determination of the concentration of the metabolites contained in intact human biopsies of 10 glioblastoma multiforme samples was achieved using one-dimensional (1)H high-resolution magic angle spinning (HR-MAS) NMR combined with ERETIC (electronic reference to in vivo concentrations) measurements. The amount of sample used ranged from 6.8 to 12.9 mg. Metabolite concentrations were measured in each sample using two methods: with DSS (2,2-dimethyl-2-silapentane-5-sulfonate sodium salt) as an internal reference and with ERETIC as an external electronically generated reference. The ERETIC signal was shown to be highly reproducible and did not affect the spectral quality. The concentrations calculated by the ERETIC method in model solutions were shown to be independent of the salt concentration in the range typically found in biological samples (0-250 mM). The ERETIC method proved to be straightforward to use in tissues and much more robust than the internal standard method. The concentrations calculated using the internal DSS concentration were systematically found to be higher than those determined using the ERETIC technique. These results indicate a possible interaction of the DSS molecules with the biopsy sample. Moreover, variations in the sample preparation process, with possible loss of DSS solution, may hamper the quantification process, as happens in one of the ten samples analysed. In this study, the ERETIC method was validated on model solutions and used in brain tumour tissues. Calculated metabolite concentrations obtained with the ERETIC procedure matched the values determined in the same type of tumours by in vivo, ex vivo and in vitro methodologies.