Total Vessel Volume Research Articles

Intravascular ultrasound study of the effect of beta-emitting ((55)Co) stents on vascular remodeling and intimal proliferation.

The aim of this study was to evaluate vessel remodeling after implantation of high-activity (mean, 41.1 +/- 1.2 microCi) beta-emitting ((55)Co) stents. Proton bombarding in cyclotron has brought the radioactivity. Intravascular ultrasound (IVUS) investigation has been completed in 10 patients. The angiographies performed at 6 months revealed restenosis > 50% in five cases (50%). IVUS analysis demonstrated an absence of remodeling behind the stent, with no changes in total vessel volume (TVV; 353.6 +/- 126.3 and 343.9 +/- 90.6 mm(3)) or plaque + media volume (PMV; 171.7 +/- 57.4 and 166.8 +/- 42.6 mm(3)). On the other hand, lumen volume (LV) within the stent decreased significantly from 181.9 +/- 80.2 to 154.6 +/- 45.2 mm(3) (P < 0.02). This was due to presence of neointimal hyperplasia (NIH) at both extremities of implanted stents. No chronic recoil of the implanted stents was found. The analysis of edges (5 mm distally and proximally to the last stent struts) showed no significant changes in TVV (187.3 +/- 62.60 and 176.9 +/- 53.5 mm(3)), but PMV increase significantly from 61.9 +/- 31.2 to 82.2 +/- 43.4 mm(3) (P < 0.04) and LV decreased from 125.2 +/- 40.7 to 94.7 +/- 22.0 mm(3) (P < 0.02). In conclusion, single (55)Co radioactive beta-emitting stents with high initial activity are effective in reducing neointimal hyperplasia only within the stent body, as measured by IVUS, and they do not solve the problem of restenosis at the stent extremities as well as at the stent edges. Edge restenosis in this high radioactive stents was mainly (from 66%) due to neointimal proliferation.

Glagov remodeling of the atherosclerotic aorta demonstrated by cardiovascular magnetic resonance: the CORDA asymptomatic subject plaque assessment research (CASPAR) project.

Aortic atherosclerosis and coronary artery disease (CAD) are closely linked. Early detection of aortic atherosclerosis with the adoption of appropriate preventive measures may therefore help to reduce mortality and morbidity related to CAD. Arterial remodeling, by which the wall adapts to physiological or pathological insults by a change in vessel size, is being increasingly recognized as an important aspect of atherosclerosis. In this prospective longitudinal study we used cardiovascular magnetic resonance (CMR) to detect aortic plaque and to study aortic wall remodeling in asymptomatic subjects. We recruited 175 healthy volunteers (49 years, 110 men) and documented their cardiovascular risk profile. Each subject underwent echocardiogram (ECG)-gated T1-weighted spin-echo imaging of the infrarenal abdominal aorta at baseline and after 2 years. Of the 175 subjects who volunteered at baseline, CMR was successful in 174 (99%), with one (0.6%) failure due to claustrophobia. At 2 years, follow-up scanning was performed in 169 subjects (97%). Infrarenal aortic plaque was identified at baseline in nine (5.2%) subjects. This was reconfirmed in all nine (100%) cases at 2-year follow-up. No new cases of infrarenal plaque were identified at follow-up. The signal characteristics of the plaque on the subtracted images of the Dixon method indicate that all plaques were fibrous. In the nine subjects with infrarenal plaque, the total plaque burden increased as assessed by the total wall volume (561 to 677 mm3, p = 0.0063). The total vessel volume also increased (1737 to 1835 mm3, p = 0.031) but there was no change in the total luminal volume (1175 to 1157 mm3, p = 0.29). Cardiovascular magnetic resonance detects subclinical aortic atherosclerosis, can follow plaque burden over time, and confirms the presence of Glagov remodeling with preservation of the lumen despite progression of plaque. Cardiovascular magnetic resonance is well suited for the longitudinal follow-up of the general population with atherosclerosis, may help in the understanding of the natural history of atherosclerosis, and in particular may help determine factors to retard disease progression at an early stage.

Antiangiogenic effects of dexamethasone in 9L gliosarcoma assessed by MRI cerebral blood volume maps.

Depending on dose, dexamethasone has been shown to inhibit or stimulate growth of rat 9L gliosarcoma and decrease the expression of vascular endothelial growth factor (VEGF), an important mediator of tumor-associated angiogenesis. We demonstrate, by constructing relative cerebral blood volume (rCBV) maps with MRI, that dexamethasone also decreases total blood volume while increasing microvascular blood volume in Fischer rats bearing intracranial 9L gliosarcoma. Animals were inoculated with 1 x 10(5) 9L gliosarcoma tumor cells. On days 10-14 after tumor cell inoculation, animals were intra-peritoneally injected with dexamethasone (3 mg/kg) over 5 days. MRI-derived gradient echo (GE) and spin-echo (SE) rCBV maps were created to demonstrate total vasculature (GE) and microvasculature (SE). After MRI studies were performed, the rat's vasculature was perfused with a latex compound. Total vessel volume and diameters were assessed by microscopy. Dexamethasone decreased the tumor-enhancing area of postcontrast T1-weighted images (P < 0.0001) and total tumor volume(P = 0.0085). In addition, there was a greater than 50% decrease in GE rCBV (total vasculature) (P = 0.007) as well as a significant decrease in total fractional blood volume, as validated by histology (P = 0.0007). Conversely, there was an increase in SE rCBV signal (microvasculature) in animals treated with dexamethasone (P = 0.05), which was consistent with microscopy (P < 0.0001). These data demonstrate that (1) dexamethasone selectively treats tumor vasculature, suggesting a vessel-size selective effect and (2) MRI-derived rCBV is a noninvasive technique that can be used to evaluate changes in blood volume and vascular morphology.

Positive geometric vascular remodeling is seen after catheter-based radiation followed by conventional stent implantation but not after radioactive stent implantation.

Recent reports demonstrate that intracoronary radiation affects not only neointimal formation but also vascular remodeling. Radioactive stents and catheter-based techniques deliver radiation in different ways, suggesting that different patterns of remodeling after each technique may be expected. We analyzed remodeling in 18 patients after conventional stent implantation, 16 patients after low-activity radioactive stent implantation, 16 patients after higher activity radioactive stent implantation, and, finally, 17 patients who underwent catheter-based radiation followed by conventional stent implantation. Intravascular ultrasound with 3D reconstruction was used after stent implantation and at the 6-month follow-up to assess remodeling within the stent margins and at its edges. Preprocedural characteristics were similar between groups. In-stent neointimal hyperplasia (NIH) was inhibited by high-activity radioactive stent implantation (NIH 9.0 mm(3)) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm(3)) compared with low-activity radioactive stent implantation (NIH 21.2 mm(3)) and conventional stent implantation (NIH 20.8 mm(3)) (P:=0.008). No difference in plaque or total vessel volume was seen behind the stent in the conventional, low-activity, or high-activity stent implantation groups. However, significant increases in plaque behind the stent (15%) and in total vessel volume (8%) were seen in the group that underwent catheter-based radiation followed by conventional stent implantation. All 4 groups demonstrated significant late lumen loss at the stent edges; however, edge restenosis was seen only in the group subjected to high-activity stent implantation and appeared to be due to an increase in plaque and, to a lesser degree, to negative remodeling. Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting.

Three-dimensional intravascular ultrasound assessment of noninjured edges of beta-irradiated coronary segments.

The "edge effect," late lumen loss at the margins of the treated segment, has become an important issue in the field of coronary brachytherapy. The aim of the present study was to assess the edge effect in noninjured margins adjacent to the irradiated segments after catheter-based intracoronary beta-irradiation. Fifty-three vessels were assessed by means of 3-dimensional intravascular ultrasound after the procedure and at 6- to 8-month follow-up. Fourteen vessels (placebo group) did not receive radiation (sham source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5 mm in length) were identified as noninjured, whereas 18 noninjured edges were selected in the placebo group. We compared the volumetric intravascular ultrasound measurements of the noninjured edges of the irradiated vessels with the fully irradiated nonstented segments (IRS, n=27) (26-mm segments received the prescribed 100% isodose) and the noninjured edges of the vessels of the placebo patients. The lumen decreased (6 mm(3)) in the noninjured edges of the irradiated vessels at follow-up (P:=0. 001). We observed a similar increase in plaque volume in all segments: noninjured edges of the irradiated group (19.6%), noninjured edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume increased in the IRS in the 3 groups. No edge segment was subject to repeat revascularization. The edge effect occurs in the noninjured margins of radiation source train in both irradiated and placebo patients. Thus, low-dose radiation may not play an important role in this phenomenon, whereas nonmeasurable device injury may be considered a plausible alternative explanation.

Volumetric remodeling of the proximal left coronary artery: Early versus late after heart transplantation

OBJECTIVESThe aim of this study was to characterize progression of cardiac allograft vasculopathy (CAV) with special respect to coronary artery geometry.BACKGROUNDAs previously shown by intravascular ultrasound (IVUS), CAV is characterized by a multifocal intimal hyperplasia. Little is known, however, about vascular remodeling processes influencing vessel geometry and luminal narrowing.METHODSIn 30 heart transplant recipients serial IVUS studies were performed at baseline (BL) and after a mean follow-up period of 12.5 ± 2.5 months. Changes in plaque, lumen and vessel volume were assessed in the proximal left anterior descending artery. Pattern of remodeling was analyzed in patients “early” (n = 15, BL study 1.4 ± 0.7 months after heart transplantation [HTX]) compared with “late” after HTX (n = 15, BL 46.1 ± 29.1 months).RESULTSPlaque volume was found to increase by a mean of 23.8 ± 25.9 mm3, not significantly different within and beyond the 1st year after HTX. Significant differences, however, were observed in changes in vessel volume with a mean decrease of −52.8 ± 70.9 mm3in the early group, whereas late follow-up group presented with an enlargement of 32.3 ± 46.0 mm3. Based on these changes, lumen volume decreased by −73.2 ± 69.8 mm3early, in contrast to a slight increase of 5.2 ± 32.6 mm3in the late group.CONCLUSIONSProgression of CAV is a complex process, modified by changes in the vascular geometry. Especially within the 1st year after HTX, luminal loss is influenced not only by an increase in plaque area but by a decrease in total vessel volume as well.

Quantitative characterization of mixing of dry powders in V‐blenders

AbstractExperiments were conducted to determine the effect of rotation rate, fill level, and total number of revolutions on the mixing performance of a V‐blender. The experiments were performed using 66‐μm red and green glass beads. Mixture uniformity was quantified after each experiment by infiltrating the mixtures with a binder, and using image analysis to examine slices of the solidfied mixture. The mixing rate (as a function of total revolutions) was not affected by changing the rotation rate between 8 and 24 rpm. The mixing rate increased significantly as the fill percentage was decreased from 60% to 40% of the total vessel volume. In a symmetric blender such as a V‐blender, the rate of mixing is limited by the rate of mass transfer across the vessel plane of symmetry orthogonal to the axis of rotation. A one‐parameter model based on the amount of material that crossed the plane of symmetry per revolution displayed good agreement with the experimental data.

A Phase-Segregated Model for Plant Cell Culture: The Effect of Cell Volume Fraction.

Plant cells are characterized by low water content, so the fraction of cell volume (volume fraction) in a vessel is large compared with other cell systems, even if the cell concentrations are the same. Therefore, concentration of plant cells should preferably be expressed by the liquid volume basis rather than by the total vessel volume basis. In this paper, a new model is proposed to analyze behavior of a plant cell culture by dividing the cell suspension into the biotic- and abiotic-phases, Using this model, we analyzed the cell-growth and the alkaloid production by Catharanthus roseus, Large errors in the simulated results were observed if the phase-segregation was not considered.

The association between tumour progression and vascularity in the oral mucosa.

Tumourigenesis in experimental models is associated with the formation of new blood vessels (angiogenesis). Recent studies have suggested that tumour angiogenic activity may be inferred in histological sections by measuring the density of the vasculature. The purpose of this study was to determine whether the transition from normal to dysplastic and neoplastic tissue in the oral mucosa is accompanied by quantitative or qualitative changes in the vascularity of the tissue, and how the estimate of vascularity is influenced by the vessel marker and method of assessment. A total of 100 specimens of normal oral mucosa, dysplastic lesions, and squamous cell carcinomas were examined. Sections were immunostained with the pan-endothelial antibodies to von Willebrand Factor (vWF) and CD31, or with an antibody to the alpha v beta 3 integrin, previously reported to be a marker of angiogenic vessels. Vascularity was quantitated by two different methods: highest microvascular density (h-MVD) and microvascular volume, as determined by point counting (MVV). The results showed that vascularity, measured by the MVV method using antibodies to either vWF or CD31, increased significantly (P < 0.0001) with disease progression from normal oral mucosa, through mild, moderate, and severe dysplasia to early and late carcinoma (76 paraffin-embedded tissues examined). In contrast, h-MVD did not discriminate between dysplastic lesions and carcinoma. A similar percentage of the total vessel volume (MVV) and density (h-MVD) were positive for alpha v beta 3 in 24 frozen tissues examined, including normal oral mucosa. It is concluded that there is a close association between vascularity and tumour progression in the oral mucosa. Morphometric analysis reflecting microvascular volume is more informative than the currently popular analysis of microvascular density. The expression of alpha v beta 3 in the vasculature of oral tissues does not necessarily reflect the presence of angiogenic vessels.

Effect of Rotational Atherectomy in Noncalcified Atherosclerotic Plaque: A Volumetric Intravascular Ultrasound Study

Objectives. This study used pre-rotational and post-rotational atherectomy volumetric intravascular ultrasound analysis to determine whether rotational atherectomy causes ablation of noncalcified atherosclerotic plaque.Background. Rotational atherectomy is currently the preferred treatment for heavily calcified coronary lesions. However, the mechanism of lumen enlargement in noncalcified lesions has not been studied in detail. Intravascular ultrasound allows detailed, cross-sectional imaging of the coronary arteries in vivo. The normal coronary artery wall, the major components of the atherosclerotic plaque and the quantitative changes in vessel, lumen and plaque cross-sectional areas and volumes that occur as a result of the atherosclerotic disease process and during transcatheter therapy can be studied in a manner otherwise not possible.Methods. Eighteen noncalcified native vessel lesions in 18 patients were imaged before and after rotational atherectomy using intravascular ultrasound systems incorporating motorized transducer pullback through a stationary imaging sheath. External elastic membrane, lumen and plaque plus media cross-sectional areas were measured every 1 mm of lesion length (for a total of 10 image slices), and external elastic membrane, lumen and plaque plus media volumes were calculated using Simpson's rule.Results. After rotational atherectomy, the minimal lumen cross-sectional area increased from 1.37 ± 0.50 to 2.99 ± 0.60 mm2 (mean value ± 1 SD, p < 0.0001). Lumen volume increased from 23.2 ± 9.0 to 38.0 ± 8.0 mm3 (p < 0.0001) as a result of a decrease in plaque plus media volume (from 102.2 ± 50.9 to 85.8 ± 47.7 mm3, p < 0.0001), with no change in total vessel (external elastic membrane) volume (125.3 ± 54.2 to 123.8 ± 52.9 mm3, p = 0.119).Conclusions. Rotational atherectomy effectively ablates noncalcified plaque in non-calcium-containing lesions.

Signs of aging are apparent in the testis interstitium of Sprague Dawley rats at 6 months of age

The present study investigated the effects of aging in the testis interstitium in Sprague Dawley rats. Rats of 3, 6 and 24 months of age were used. Testes of rats ( n = 5) were fixed by whole body perfusion using a fixative containing 2.5% glutaraldehyde in cacodylate buffer, processed and embedded in eponaraldite. Using 1 μm sections stained with methylene blue, qualitative and quantitative morphological studies were performed. Purified Leydig cell preparations, obtained by collagenase digestion followed by elutriation and density gradient centrifugation, were used to determine luteinizing hormone (LH; 100 ng/ml) stimulated testosterone secretory capacity per Leydig cell in vitro. Testosterone levels in the incubation medium, and testosterone and luteinizing hormone levels in serum of these three groups of rats were determined via radioimmunoassay. Morphological studies revealed that Leydig cells were more abundant in the testis interstitium at 6 and 24 months when compared to 3 months. Moreover, collagen fiber bundles were more frequently observed in the testis interstitium at older ages. Blood vessels of the testis interstitium in 24-month-old rats frequently showed partial and complete occlusion of their lumen and thickening of vessel walls. This feature was also present at 6 months, but less frequently. The results of the sterological studies revealed that the volumes of seminiferous tubules, interstitium and Leydig cells per testis was significantly higher ( P < 0.05), at 6 and 24 months of age than those at 3 months. Moreover, volume of macrophages per testis was observed to be significantly higher ( P < 0.05) at 6 months when compared to 3 and 24 months, and volume of connective tissue cells per testis was observed to be significantly lower ( P < 0.05) at 6 and 24 months when compared to 3 months of age. No significant difference ( P > 0.05) was observed for the volume of lymphatic space per testis in the three age groups studied. Volume of interstitial blood vessels per testis was not significantly different at 3 and 6 months of age, but a significantly greater ( P < 0.05) volume was observed at 24 months. However, at 6 and 24 months, only 71% and 31% of the total blood vessel volumes respectively had completely open lumen in them; the rest of the blood vessels were either partially (12.5% at 6 months and 17% at 24 months) or completely (16.5% at 6 months and 52% at 24 months) occluded. The number of Leydig cells per testis was doubled at 6 and 24 months of age compared to 3 months. The average volume of a Leydig cell was not significantly different between 3 and 6 months of age, however, at 24 months a significantly lower ( P < 0.05) value was observed. LH stimulated testosterone secretory capacity per Leydig cell in vitro was reduced by 50% at 6 months of age compared to 3 months; a further significant ( P < 0.05) reduction was observed at 24 months. Serum testosterone and LH levels were not significantly different between 3 and 6 months of age but at 24 months a significantly lower ( P < 0.05) value was observed for both of these hormones. In summary, the present study demonstrated many changes in the components of the testis interstitium in the aged Sprague Dawley rat. Modifications in the blood vessels and the occurrence of abundant collagen fibers in the interstitial space could possibly contribute to the reduced testosterone secretory capacity per Leydig cell with advancing in age. The observed Leydig cell hyperplasia could be suggested as a compensatory effort to maintain the normal androgen status of the aged rat, which is rather successful at 6 months but unsuccessful at 24 months. This investigation further revealed that these characteristic changes in the aged testis interstitium at 24 months are also present to some extent at 6 months of age in Sprague Dawley rats, suggesting that aging of the testis in this strain of rats commences early in life.

Quantitative analysis of the fine vascular anatomy of articular ligaments.

An image analysis technique has been developed to quantitatively describe the fine vascular patterns observed in ligament tissue. The longitudinal orientational distribution and total vessel volume of India-ink-perfused blood vessel segments in normal and healing ligaments were determined. The methods involved special vascular preparation of adult rabbit knee medial collateral ligaments (MCL) by India-ink perfusion. Black and white microscope images of ink-perfused tissue sections were subjected to a thresholding procedure to binarize digitized ligament images, which were then skeletonized and analyzed for directional distribution based on the least-squares technique. Analysis of medial collateral ligaments in New Zealand White rabbits using this method has shown that scarred tissue is more vascular and has a more chaotic angular distribution of blood-vessel segments than normal ligament tissue.

Detection of moving flow separation in pulsatile flow and the degree of stenosis by power of Doppler shift signals.

Power ratios were derived from the principle of ultrasonic Doppler velocimetry to determine a ratio of the volume of vortices to the total vessel volume under the ultrasonic beam. This ratio also equals the ratio of the cross-sectional area of vortices to the vessel lumen. In vitro pulsatile flow experiments were performed in a Reynolds number range of 1,230-4,320 with axisymmetric constrictions with area reductions of 55%, 65%, 70%, and 85% to model carotid stenosis. Flow separation downstream from the model stenoses was detected, and the power ratio fluctuated when vortices with the forward- and reverse-flow velocity components passed by the measurement position. The power ratio estimated the degree of stenosis within 10% of error. Ensemble average of the power ratio was computed to obtain the statistically averaged separated flow region. The moving flow reattachment point was revealed downstream from the 85% stenosis at a Reynolds number of 900.

Determination of volume of vortices in poststenotic pulsatile flow by ultrasonic Doppler power ratio and spectrum analysis

Based on the principle of ultrasonic Doppler flowmetry, a power ratio was derived from independent forward and reverse flow Doppler shift signals to measure a ratio of the volume of vortices to the total vessel volume in poststenotic separated flow. The ratio was also proportional to the ratio of the cross-sectional areas of vortices to the vessel lumen. In vitro pulsatile flow experiments were performed to test the methodology and to study flow separation and vortex shedding downstream from model stenoses. The averaged flow cross-sectional area ratio linearly correlated ( r=0.91) with the actual area reduction of the stenosis.

Microvessel surface area, density and dimensions in brain and muscle of the cephalopod Sepia officinalis

The microvasculature of brain and muscle in the cuttlefish Sepia was studied with stereological techniques to provide information about the surface area for exchange at the blood-tissue interface which was necessary for a parallel study of the permeability of the blood-brain barrier in Sepia . Microvessel density, length, dimensions and volume fraction, and the radius of the ‘Krogh cylinder’ of tissue supplied by each microvessel were also estimated. Vertical lobe (VL) and optic lobe (OL) of brain, outer collar valve muscle (VM) and tentacle muscle (TM) were analysed in 1 μm sections of aldehyde-fixed, Epon-embedded material. ‘Microvessels’ (diameter less than 20 μm) had a surface area density S v (in the order VL, OL, VM, TM) of 134, 176, 67.9 and 13.8 cm 2 cm -3 respectively. The numbers of microvessels per unit area tissue, Q A , were 211, 395, 157 and 43 mm -2 respectively. The length density of microvessels J V = 2 x Q A . The microvessel density was significantly greater in synaptic neuropil (NP) than neuron cell body (CB) zones. Total vessel volume density V V was 3.49, 4.73, 1.88 and 0.28%, in good agreement with previous estimates using intravascular tracers. Mean microvessel diameter d̄ was in the range 4.1-6.5 μm (mode 3.9-4.9 μm). The radius of the Krogh cylinder, R, was 28, 20, 32 and 61 μm. Calculations with the Krogh-Erlang equation show that brain and valve muscle are unlikely to be hypoxic under physiological conditions, while tentacle muscle may be. The vascular parameters correlate well with the known biochemistry of cephalopod tissues. This study represents a detailed analysis of the microvasculature in a complex invertebrate and permits useful comparisons with vertebrate tissues. Values for microvascular S V , Q A , J V and d̄ in Sepia brain are similar to those of the rat, while Sepia muscle vascularity is less than in the rat.

Vascular changes associated with growth of primary and transplantable pancreatic adenocarcinomas induced in Syrian golden hamsters by N-nitrosobis(2-oxopropyl)amine (BOP) and N-nitrosobis(2-hydroxypropyl)amine (BHP)

Microangiographic and histological methods were used to characterize vascular structure of primary and transplantable pancreatic adenocarcinomas induced by propylnitrosamines in Syrian golden hamsters. Originally of well-differentiated tubular morphology, serial transplantation subcutaneously to the back region was not associated with change in histopathological pattern or increase in invasive or metastatic potential. In contrast, pancreatic subserosal grafts displayed prominent invasion of surrounding tissues. Whereas primary tumors induced by N-nitrosobis(2-oxopropyl)amine (BOP) and those transplanted subserosally were characterized by hypovascularity, subcutaneous transplantation resulted in hypervascular tumors. Encasement, which is defined as invasion of normal arteries by the tumor, showing uneven caliber, irregular outline, appeared on earlier microangiographic findings rather than luminal irregularity, which is change of tumor vessels in neovascularization and occurs in tumor blood vessels subsequent to transplantation. The vascular component of subcutaneously transplanted tumors had a total vessel length ranging from 9.2 +/- 0.7 mm to 18.1 +/- 1.1 mm, a total vessel surface from 2.5 +/- 0.4 mm2 to 9.3 +/- 0.6 mm2 and a total vessel volume from 0.07 +/- 0.02 mm3 to 0.49 +/- 0.04 mm3, indicating that the vessels were of relatively large diameter and short length.

Vascular structure of the C3H mammary carcinoma, the B16 melanoma and the Lewis lung carcinoma in syngeneic, conventional mice and congenitally athymic mice

The vascular system of three commonly used murine experimental tumours, the C3H mammary carcinoma, the B16 melanoma and the Lewis lung carcinoma, in syngeneic (C3D2F1/Bom or C57BL/6J/Bom) and athymic (BALB/c/nu/nu/Bom) mice was studied. The main vascular characteristics of each tumour, i.e. the mean vessel diameter, the total vessel volume and the distribution of the total vessel volume among vessels with different diameters, did not change upon transplantation from conventional to athymic mice. However, the length of vessels with diameters in the range 5–15 μm was for all tumours shorter in athymic than in conventional mice. The vascular volume of the B16 melanoma per unit histologically intact tumour volume in athymic mice (0.040 ± 0.004) was considerably larger than that of five human melanoma xenografts previously studied (0.009 ± 0.001 to 0.022 ± 0.002). This difference was mainly due to occurrence of vessels with diameters in the range 55–145 μm in the B16 melanoma; vessels which were generally not observed in the human melanoma xenografts.

Growth and vascular structure of human melanoma xenografts.

The growth and the vascular structure of five human melanomas grown in athymic nude mice were studied. Four growth parameters (tumour volume doubling time, fraction of cells in S-phase, growth fraction, cell-loss factor) were analysed against each of four vascular parameters (length of vessels with diameters in the range 5-15 micron, total vessel length, total vessel surface, total vessel volume--all per unit of histologically intact tumour volume). Statistically significant linear correlations between the parameters were found for any of the combinations. However, there was a consistent trend in the data: the tumour volume doubling time and the cell-loss factor tended to decrease while the fraction of cells in S-phase and the growth fraction tended to increase with increasing vascular density, whichever vascular parameter was considered. This finding indicates that the vascular density is among the factors which are decisive for the growth rate of tumours. However, the present work does not exclude the possibility that intrinsic properties of the tumour cells may also be important.

Vascular structure of five human malignant melanomas grown in athymic nude mice.

The vascular structure of 5 human malignant melanomas grown in athymic nude mice was characterized. The vessels were filled with a radio-opaque medium administered via the abdominal aorta of the mice. X-ray images, obtained from 720 micrometers-thick tumour sections, provided qualitative information on the vascular structure of the tumours. Histograms for vessel length, surface, and volume as a function of vessel diameter were obtained by stereological analysis of 2 micrometers-thick sections. The volume fraction of necrotic tissue in the tumours was also determined by stereological analysis. The 5 melanomas exhibited individual, characteristic vascular structures as well as individual, characteristic necrotic fractions. The total vessel length ranged from 32 +/- 2 to 80 +/- 4 mm, the total vessel surface from 1.6 +/- 0.1 to 3.8 +/- 0.2 mm2, and the total vessel volume from 0.009 +/- 0.001 to 0.022 +/- 0.002 mm3--all values per mm3 histologically intact tumour tissue. The necrotic fractions ranged from 30 +/- 1 to 49 +/- 4%, and tended to be higher in the poorly than in the well-vascularized melanomas. The volume doubling times ranged from 4.2 to 21.6 days. Melanomas with short volume-doubling times had lower necrotic fractions and tended to be better vascularized than those with long volume-doubling times.