Intra-operative characterization of gliomas by near-infrared spectroscopy: possible association with prognosis.

BACKGROUND: Growth and expansion of gliomas are highly dependent on vascular neogenesis. An association of microvascular density and tumour energy metabolism is assumed in most human gliomas. The purpose of this investigation was to characterize a series of gliomas by intra-operative near-infrared spectroscopy (NIRS), and to elucidate the relationship between microvascular blood volume (BV), oxygen saturation (SaO(2)), histology and patient survival. METHOD: The study included 13 patients with gliomas, in whom complete tumour resection according to postoperative magnetic resonance imaging criteria was achieved. Intra-operatively, one low grade astrocytoma, five anaplastic astrocytomas and seven glioblastomas with the ipsilateral cortex were investigated by NIRS revealing capillary BV (total haemoglobin) and SaO(2). Intratumoural BV (tBV) and SaO(2) (tSaO(2)) were additionally used in relation to histology and survival. FINDINGS: The mean tBV of the astrocytomas was 4.96 mg/ml compared to 18.40 mg/ml in the glioblastoma group. Mean tSaO(2) was 36% in the astrocytoma group and 52% in the glioblastomas, respectively. Both tBV and tSaO(2) were significantly higher (p<0.01) in the glioblastoma group. Median survival time was shortest for patients with glioblastoma (12.5 months), with tBV >10/mg/ml (10 months), and tSaO(2) >50% (10 months). Longest median survival times were observed in the astrocytoma group (32.5 months), in patients with Tbv <10/mg/ml (30 months), and tSaO(2) <50% (27.5 months). The differences were highly significant (p<0.01). INTERPRETATION: Intra-operative characterization of gliomas by NIRS is feasible. High tBV represents extensive angiogenetic activity of the tumour, whereas high tSaO(2) may be result of non-oxidative glucose metabolism with less oxygen extraction from the capillary bed of the tumour. However, the extent of tBV and tSaO(2) are both of possible prognostic value thus resulting in additional information about the tumour.

In-vivo measurement of cytochrome using NIRS during acute focal cerebral ischaemia and reperfusion in rats.

OBJECTIVES: Near-infrared spectroscopy (NIRS) based technology allows in-vivo monitoring of focal tissue cytochrome aa3 (cytochrome-c-oxidase). The aim of this study was to assess early cell alteration during acute focal cerebral ischaemia and reperfusion. METHODS: Focal cerebral ischaemia was induced in 12 rats using an endovascular occlusion technique of the middle cerebral artery (MCA). Occlusion time was 60 minutes followed by reperfusion for another 60 minutes. Monitoring of oxygen saturation (SO2) and oxidized cytochrome complex (oxid. Cytaa3 ) was performed by NIRS via a parietal burr hole before (baseline), during occlusion and reperfusion. Twenty-four hours after MCA occlusion (MCAO) infarction was confirmed by TTC staining. RESULTS: In all animals SO2 and oxid. Cytaa 3 immediately decreased to zero during occlusion indicating complete ischaemia. According to the results of NIRS measurements during reperfusion animals were subdivided into two groups. All animals of group A demonstrated identical or even higher levels of SO2 and oxid. Cytaa3 compared to baseline. On the contrary, both parameters in group B remained at a distinct lower level compared to baseline (p < 0.05). Average reperfusion/baseline ratios for SO2 and oxid. Cytaa 3 were 0.8 (+/- 0.4) and 0.4 (+/- 0.2), respectively. The results of TTC-staining were distributed to the above mentioned two groups as follows: group A, only lesions in the basal ganglia or little cortical infarction (n = 8); group B, lesions in the basal ganglia and cortical area (n =4). CONCLUSIONS: After 1 hour MCAO a subgroup of animals with associated cortical infarction was identified, whose oxid. Cytaa3 values did not reach baseline values during reperfusion indicating early intracellular disturbance.

NIR reflection measurements of hemoglobin and cytochrome aa3 in healthy tissue and tumors. Correlations to oxygen consumption: preclinical and clinical data.

OBJECTIVES: A new near infrared reflectance spectroscopy based technology (MULTISCAN OS 10/30) for non-invasive measurements of tissue oxygenation allows detection of absolute tissue hemoglobin concentration and saturation values in real time. METHODS: MULTISCAN OS 10/30 scans a tissue sector of defined geometry at 400 to 1200 nm wavelength with 0.3 nm intervals at a scan rate of up to 400 Hz in reflection mode. The newly developed algorithms are based on the entropy pattern of photons and allow the detection of absolute values of total hemoglobin (tHb), deoxy- (Hb) and oxy-hemoglobin (HbO2) in mg/ml tissue as well as tissue oxygen (saturation = tiSO2) in the range of 0 to 100% in real time. Cytochrome aa3 (Cyt) can be monitored simultaneously. RESULTS: Physiological Stimulation. Clamping experiments at the finger of volunteers, in the intestine of a pig, in the kidney of mice and rats showed a very fast, sensitive and tissue specific reaction. Changes in breathing and/or anesthesia conditions were immediately followed by corresponding changes of tissue oxygenation (brain, finger, skin). Simultaneous measurements of oxygen (HbO2), and cytochrome showed a strong correlation between both parameters. For validation purposes parallel polarographic measurements (pO2 measurements) were performed in mice. Furthermore angiographic data of patients as well as NMR/I data were compared with the NIR spectroscopy findings. Tumor Measurements. Patients with tumors of different origins showed significantly different oxygen values. The lowest level was found in glioblastoma (< 10% sat, < 1.0 mg/ml tHb), whereas renal carcinoma showed tremendously increased values (> 90% sat, > 5.0 mg/ml tHb). In contrast the surrounding healthy kidney tissue was significantly less oxygenated and perfused compared to the tumors. Oxygen Consumption Measurements. Oxygen consumption was measured in 16 patients after ligation of the blood supply (A. and V. renalis) to the kidney affected by tumor. All tumors showed a significantly lower consumption rate compared to the healthy tissue. These findings were controlled by animal experiments of human renal carcinomas on nude mice. The same results were obtained under these experimental conditions. CONCLUSION: MULTISCAN OS 10/30 is a new and useful tool for in vivo characterization of oxygen and cytochrome in healthy and tumor tissues. In many clinically relevant situations oxygen measurements can be helpful and support the clinical routine diagnostics.