Tumour blood flow: measurement and manipulation for therapeutic gain

Sagar, Stephen M.; Klassen, Gerald A.; Barclay, Katherine D.; Aldrich, John E.

doi:10.1016/0305-7372(93)90009-g

Cited by 38 publications

(15 citation statements)

References 193 publications

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“…The spatial sampling is unfortunately too coarse to capture the details of the spatial temperature gradients associated with conductive heat removal. In order to estimate perfusion based on the BHT, the conductivity is assumed to be either negligible or known (4,5,8,9,(15)(16)(17). Another approach is to lump conductivity and perfusion into a single mea-sure, known as the "effective conductivity," from which the estimation of perfusion is attempted (12,18).…”

mentioning

confidence: 99%

Tissue thermal conductivity by magnetic resonance thermometry and focused ultrasound heating

Cheng

Plewes

2002

Magnetic Resonance Imaging

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Purpose:To investigate the combined use of magnetic resonance (MR) temperature imaging and focused ultrasound (FUS) for the noninvasive determination of tissue thermal properties. Materials and Methods:Brief, spatial impulses of temperature elevation were created in tissue using a spherical, air-backed transducer operating at 1.68 MHz and measured using MR temperature imaging in a 1.5-Tesla clinical scanner. A novel technique based on thermal washout is applied in an analysis of the acquired MR temperature images to estimate tissue thermal conductivity and perfusion.Results: Numerical simulations and experiments in vitro and in vivo demonstrate that thermal conductivity can be measured to within 10% of the true value with MR thermometry at 1.5 Tesla. With the temperature precision available at 1.5 Tesla, however, robust perfusion estimation is feasible only in highly perfused organs or tumors. Conclusion:This study has developed a method for determining tissue thermal properties specific to the patient and organ at the site of interest, and allows repeated application. This capability is relevant in thermal therapy planning of tumor ablation using MR-guided FUS systems.

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confidence: 99%

Tissue thermal conductivity by magnetic resonance thermometry and focused ultrasound heating

Cheng

Plewes

2002

Magnetic Resonance Imaging

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“…Many different classes of vasoactive agents have been tested in tumours and the results have been reviewed previously (Jain and Ward-Hartley, 1984;Sagar et al, 1993).…”

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confidence: 99%

Reduced capacity of tumour blood vessels to produce endothelium-derived relaxing factor: significance for blood flow modification

Tozer

Prise²,

Bell³

et al. 1996

Br J Cancer

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Summary The effect of nitric oxide-dependent vasodilators on vascular resistance of tumours and normal tissue was determined with the aim of modifying tumour blood flow for therapeutic benefit. Isolated preparations of the rat P22 tumour and normal rat hindlimb were perfused ex vivo. The effects on tissue vascular resistance of administration of sodium nitroprusside (SNP) and the diazeniumdiolate (or NONO-ate) vasodilators Constitutive and inducible isoforms of nitric oxide synthase (cNOS and iNOS respectively) have been detected in both experimental and human tumours (Buttery et al., 1993; Chhatwal et al., 1994;Cobbs et al., 1995;Thomsen et al., 1994Thomsen et al., , 1995. Competitive inhibition of NOS, using analogues of L-arginine at high doses, has been shown to decrease blood flow and energy status of experimental tumours and enhance the activity of bioreductive drugs (Andrade et al., 1992;Tozer et al., 1995;Wood et al., 1993, Correspondence: GM Tozer Received 2 April 1996; revised 11 July 1996; accepted 16 July 1996 1994). However, the capacity for EDRF production in tumours is unknown. Any difference from normal would provide a potential means of selectively modifying tumour blood flow for therapeutic benefit.The aims of this study were (1) to determine the sensitivity of tumour vs normal tissue blood vessels to the vasodilatory effect of NO; and (2) to determine the capacity of tumour vs normal tissue endothelial cells for production of EDRF. To this end, isolated preparations of the rat P22 tumour and normal rat hindlimb were perfused ex vivo. The effects on vascular resistance of administration of the NO donors SNP and NOC-7 (endothelium-independent vasodilators) were compared with the effects of administration of ACh (an endothelium-dependent vasodilator) in tumour and normal tissue. Some of the results for tumour alone have appeared in preliminary form as part of conference proceedings . Materials and methods TumoursEarly generations of the P22 transplanted rat carcinosarcoma were used for these experiments. Tissue-isolated tumours, whose vascular supply was derived solely from the superior epigastric vascular pedicle, were grown in the right inguinal fat pad of 10 to 11-week-old male BD9 rats. The method used was essentially as described previously (Tozer et al., 1994), except that no attempt was made to physically enclose the growing tumour to prevent vessel ingrowth from surrounding normal tissue. Instead, the surgically prepared fat containing a small (approximately 1 mm3) piece of donor tumour was loosely sutured in position in the inguinal cleft in order to prevent twisting of the vascular pedicle but allow movement of the growing tumour within the cleft. This technique results in a lower incidence of inflammation than that resulting from enclosure of the growing tumour in silicon [as used previously (Tozer et al., 1994)], while retaining a capacity for preventing vessel ingrowth from surrounding normal tissue. Tumours were used for experimentation when their vascular supply was seen to der...

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“…We are not aware that the laser Doppler method has been previously applied to measurement of adipose tissue blood flow. The method has been applied to skin (9), myocardium (6), tumor (11) and vessel blood flow including veins (2).…”

Section: Discussionmentioning

confidence: 99%

“…The method used in this study was developed in our laboratory and has been adapted to measurement of coronary venous blood flow (2), adipose tissue flow (7), tumor blood flow (11), and myocardial tissue blood flow (6). It is based upon the principle that the wave length of monochromatic laser light is phase shifted proportional to velocity of the particle reflecting the light.…”

Section: Adipose Blood Flow Measurementmentioning

confidence: 99%

Body Position, Age and Mass Effect of Adiposity on Adipose Tissue Red Cell Flux in Morbid Obesity

Klassen¹,

Janigan²,

Paton³

et al. 1996

Obesity Research

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Objective: To measure red cell flux of adipose tissue in morbidly obese patients' pannus in the upright and supine position to determine factors which would render the lower pannus susceptible to ischemic necrosis. Design: A cohort study of morbidly obese subjects without ischemic necrosis. Setting: University teaching hospital. Patients: Twenty‐three consecutive morbidly obese patients referred for gastroplasty. Measurements: Red cell flux, measured as RMS voltage by a laser Doppler velocimeter. An optical fiber with a tip diameter of 250μ was inserted into the upper and lower pannus and output recorded in the upright and supine positions. Other variables recorded were age, BMI, blood pressure and serum lipids. Results: Adipose tissue red cell flux demonstrates considerable spatial and temporal heterogeneity from subject to subject and in various locations in the pannus. No differences in red cell flux were detected in response to change in position. However, regression analysis demonstrated that the gradient between the upper and lower abdomen in the supine position was increasingly positive with age and in the upright position it was increasingly positive with increasing weight or BMI. Conclusions: These data suggest that red cell flux is heterogeneously distributed in the abdominal pannus and is not greatly influenced by body position. However, with increasing age and adiposity there is a gradient for decreased red cell flux to the lower portion of the pannus. This may be a factor in rendering this part of the pannus prone to ischemic fat necrosis.

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Tumour blood flow: measurement and manipulation for therapeutic gain

Cited by 38 publications

References 193 publications

Tissue thermal conductivity by magnetic resonance thermometry and focused ultrasound heating

Tissue thermal conductivity by magnetic resonance thermometry and focused ultrasound heating

Reduced capacity of tumour blood vessels to produce endothelium-derived relaxing factor: significance for blood flow modification

Body Position, Age and Mass Effect of Adiposity on Adipose Tissue Red Cell Flux in Morbid Obesity

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