A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT.

This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of (10)B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak (10)B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

CBIT--context-based image transmission.

Few networks offer sufficient bandwidth for the transmission of high resolution two- and three-dimensional medical image sets without incurring significant latency. Traditional compression methods achieve bit-rate reduction based on pixel statistics and ignore visual cues that are important in identifying visually informative regions. This paper describes an approach to managing image transmission in which spatial regions are selected and prioritized for transmission so that visually informative data is received in a timely manner. This context-based image transmission (CBIT) scheme is a lossless form of progressive image transmission (PIT) in which gross structure, represented by an approximate iconic image, is transmitted first. Each part of this iconic image is progressively updated, using a simple set of rules that take into account viewing requirements. CBIT is realized using knowledge about image composition to segment, label, prioritize, and fit geometric models to regions of an image. Tests, using neurological images, show that, with CBIT, a valuable transmitted image is received with a latency that is about one-tenth that of traditional PIT schemes. Frequently, the necessary regions of the image are transmitted in about half the time taken to transmit the full image.

Intradural, extramedullary spinal cord compression from tuberculous granuloma.

A 19-year-old girl presented with acute cord compression following treatment for tuberculous meningitis. Magnetic resonance imaging showed a posterior compressive lesion between T1 and T4. At laminectomy, an intradural extramedullary tuberculous granuloma was excised. To our knowledge, this is the first report of spinal cord compression occurring from a subdural tuberculous mass.

Peri-tumoural hypoxia in human brain: peroperative measurement of the tissue oxygen tension around malignant brain tumours.

Malignant brain tumours contain focal hypoxic areas that may increase their resistance to chemotherapy and radiotherapy. Following surgical excision, the peri-tumoural area will contain residual viable tumour cells, and this area is therefore the logical site for subsequent therapy. The new bioreductive agents are metabolized under hypoxic conditions to produce a cytotoxic species. Peroperative peri-tumoural micro-polarographic measurements have been made to establish the oxygen environment of this region and to determine whether the hypoxic conditions might allow for bioreductive drug activation. The micro-polarographic method is described and results are presented for "normal" white matter (8 patients) to allow comparison with peri-tumoural brain (8 patients) before and after removal of the tumour. The results suggest that peri-tumoural brain (median pO2 10.8 mmHg, 18% pO2 < 2.5 mmHg) is markedly hypoxic in comparison with the "normal" brain (median pO2 15.3 mmHg, less than 2% < 2.5 mmHg), and that surgery improves peri-tumoural oxygenation towards that of the "normal" white matter. It is concluded that the hypoxic peri-tumoural area can provide the conditions under which bioreductive agents may be activated.

Does tumour related oedema contribute to the hypoxic fraction of human brain tumours?

Focal hypoxia has been demonstrated and is known to contribute to the resistance of malignant brain tumours to radiation and chemotherapy. Using dynamic needle micro-polarography and tissue morphometry on biopsy specimens, the relationship between the effect of oedema on tissue structure and tissue pO2 was investigated in 24 patients undergoing craniotomy for tumour decompression. An inverse correlation (r = -0.84) was found for intercapillary distance and pO2 levels in peritumoural white matter, but this was less marked (r = -0.22) in tumour, probably as a result of sampling difficulties from tissue heterogeneity. Comparison of maximum pO2 levels in oedematous peritumoural white matter with those in tumour suggests that peritumoural oedema is unlikely to contribute to tumour hypoxia.