Tumour microcirculation as a target for hyperthermia

Abstract

A great number of investigators have, independently, shown that tumour blood flow is affected by a hyperthermic treatment to a larger extent than normal tissue blood flow. While the majority of the studies on experimental tumours show a decrease and even a lapse in blood flow within the microcirculation during or after hyperthermia, the data on human tumours are less conclusive. Some of the investigators do not find a decrease in circulation, while others do. Obviously, this is an important field of investigation in the clinical application of hyperthermia because a shut down of the circulation would not only facilitate tumour heating (by reducing venous outflow, this reducing the 'heat clearance' from the tumour), but would also facilitate tumour cell destruction. The same holds for alterations that occur subsequently to the circulatory changes, like a heat-induced decrease of tissue pO2 and pH. If the frequently reported circulatory collapse of the tumour circulation could selectively be stimulated by, e.g. acidification or by vasoactive agents, hyperthermic treatment of patients would possibly be greatly facilitated and intensified. In hyperthermic tumour therapy a number of complex processes and interactions takes place, especially when the treatment is performed in combination with radiation therapy. One of them represents the group of processes related to the random probability of cell sterilization of individual tumour cells resulting in exponential survival curves which are typically evaluated with e.g. cell survival assays. This aspect has not been the issue of this paper. The other group of processes deals with the heat-induced changes in the micro-physiology of tumours and normal tissues which, as discussed before, may not only enhance the exponential cell kill, but which may also culminate in vascular collapse with the ensuing necrosis of the tumour tissue in the areas affected. If this takes place, a process of bulk killing of tumour cells results, rather than the random type of cell sterilization. At present it is not clear to what extent the various separate mechanisms contribute to the total effect of tumour control. With all these considerations in mind, one should be aware of the fact that effects, secondary to heat-induced vascular stasis alone will never be efficient enough to eliminate all tumour cells, even though a heat reservoir is created. This is so because some malignant cells will inevitably have already infiltrated normal, surrounding structures and will therefore not be affected by changes in the tumour vascular bed.(ABSTRACT TRUNCATED AT 400 WORDS)

Tissue thermal conductivity by magnetic resonance thermometry and focused ultrasound heating

“…Following Cline et al (25), these focusing patterns can be approximated with elliptical Gaussian functions with radial and axial radii r o and z o , respectively, corresponding to about 60% of the maximum intensity, from which an exact analytic solution to Eq. [1] is obtained (25):…”

“…Equation [1] assumes that heat is removed by two mechanisms: conduction, which reduces spatial temperature gradients, and perfusion, which is modeled as a spatially uniform heat sink. The nondirectional perfusion term represents the collective effect of the numerous small vessels in the capillary bed, which is the assumed site of thermal equilibration between blood and tissue (11).…”

“…The assumption of an impulse heat source in space and in time lends a simple analytic solution to Eq. [1]. This ideal impulse can be approximated using a spatially FUS source (Fig.…”

“…Local tissue thermal conductivity and blood perfusion, however, play important roles as they can alter the temperature distributions achieved in the tissue (1). Because conductivity and perfusion are tissue-specific and likely also patient-specific parameters, ensuring adequate thermal treatment is a challenging task.…”

The potential for prazosin and calcitonin gene-related peptide (CGRP) in causing hypoxia in tumours

“…Tumours are thought to have long, tortuous, leaky vessels with frequent A-V shunts, lack of smooth muscle and probably no innervation. Interstitial pressure tends to be high due to leaky vessels (Wiig et al, 1982) and lack of lymph drainage (see Reinhold & Endrich, 1986 for review). The response of the vasculature of a tumour to a vasodilator is likely to be different from that of a normal tissue for two reasons (Chan et al, 1984).…”