Biomedical subjects

C M Sehgal

Publications and source records attributed to C M Sehgal.

At least 19 recordsLinked to original sources

PubMed2005

Diffuse boundary extraction of breast masses on ultrasound by leak plugging.

We propose a semiautomated seeded boundary extraction algorithm that delineates diffuse region boundaries by finding and plugging their leaks. The algorithm not only extracts boundaries that are partially diffuse, but in the process finds and quantifies those parts of the boundary that are diffuse, computing local sharpness measurements for possible use in computer-aided diagnosis. The method treats a manually drawn seed region as a wellspring of pixel "fluid" that flows from the seed out towards the boundary. At indistinct or porous sections of the boundary, the growing region will leak into surrounding tissue. By changing the size of structuring elements used for growing, the algorithm changes leak properties. Since larger elements cannot leak as far from the seed, they produce compact, less detailed boundary approximations; conversely, growing from smaller elements results in less constrained boundaries with more local detail. This implementation of the leak plugging algorithm decrements the radius of structuring disks and then compares the regions grown from them as they increase in both area and boundary detail. Leaks are identified if the outflows between grown regions are large compared to the areas of the disks. The boundary is plugged by masking out leaked pixels, and the process continues until one-pixel-radius resolution. When tested against manual delineation on scans of 40 benign masses and 40 malignant tumors, the plugged boundaries overlapped and correlated well in area with manual tracings, with mean overlap of 0.69 and area correlation R2 of 0.86, but the algorithm's results were more reproducible.

Algorithms↗

PubMed2003

Local control of high-grade gliomas with limited volume irradiation versus whole brain irradiation.

INTRODUCTION: To evaluate the role of limited field radiation therapy in the management of high-grade gliomas and glioblastoma multiforme (GBM). MATERIAL AND METHODS: From July '96 to January '98, 50 newly diagnosed patients of high-grade gliomas (Grade III and IV) and glioblastoma multiforme who underwent surgery in the form of partial, sub-total or near-total excision as the primary treatment were enrolled in this study. The patients were randomized to receive two different postoperative external radiation protocols, Study Group A: Localized field external radiotherapy 50 Gy/25#/5 wks followed by Boost 10 Gy/5#/1 wk, Control Group B: Whole brain external radiotherapy 40 Gy/20#/4 wks followed by Boost 20 Gy/10#/2 wks by localized field. RESULTS: 20/25 (80%) patients in the study group and 14/25 (56%) patients in the control group showed improvement in their Karnofsky Performance Status (KPS). Thus a significant difference in the performance status was noted in favor of limited field irradiation. No significant difference in the local response was seen between the two groups after radiotherapy. Six months progression-free survival of the study group was 44% as compared to 26% in the control group. Six months overall survival was 66.67% in the study group and 50.72% in the control group (P<0.01). Maximum recurrences were noticed within 2 cm of the original tumor margin in both the groups. CONCLUSIONS: Although local control and survival of the patient in both the groups were same, performance status definitely improved in patients treated with localized field irradiation only.

Brain Neoplasms↗

PubMed2001

Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations.

Noninvasive monitoring of antiangiogenic therapy was performed by serial power Doppler ultrasound imaging of murine tumors treated with recombinant interleukin 12, the results of which were correlated with assessments of tumor vascularity by microscopy. Growth of established K1735 tumors, but not of IFN-gamma-unresponsive K1735.N23 variants, was suppressed by treatment. Serial Doppler imaging of K1735 tumor vascularity during treatment revealed a progressive change from a diffuse perfusion pattern to a more punctate distribution. Quantitative analysis of the images revealed that color-weighted fractional average, representing overall tumor perfusion, consistently decreased in these tumors, primarily because of a decrease in fractional tumor cross-sectional area carrying blood flow. In contrast, these parameters increased in nonresponsive tumors during treatment. Confocal microscopy of thick tumor sections revealed a reduction in the density and arborization of vessels labeled in vivo by fluorochrome-conjugated lectin with effective treatment. Immunohistological examination of thin tumor sections confirmed the preferential loss of small vessels with successful therapy. Similar changes in tumor vascular anatomy and perfusion were also observed during recombinant interleukin 12 treatment of two other responsive murine tumor types. These results indicate that power Doppler ultrasound is a sensitive, noninvasive method for reporting functional consequences of therapy-induced vascular anatomical changes that can be used to serially monitor tumor perfusion and efficacy of antivascular therapy in clinical trials.

Animals↗

PubMed2001

Interreader variability and predictive value of US descriptions of solid breast masses: pilot study.

RATIONALE AND OBJECTIVES: This study evaluated the specificity of ultrasound (US) characteristics of solid breast lesions and the interreader variability in their interpretation. MATERIALS AND METHODS: In 61 patients, 70 sonographically visible solid masses, scheduled for biopsy because of findings from conventional imaging, were prospectively and sequentially accrued for evaluation. Three readers interpreted the sonograms and described the solid masses in terms of established US characteristics. The specificity and positive predictive value (PPV) for each characteristic were calculated by comparing US findings with biopsy findings, and interreader variability was evaluated. Five assessment categories were developed to guide recommendations for patient care. The relative performance of each reader was assessed by measuring the PPV for each assessment category and by measuring the area under the receiver operating characteristic curve. RESULTS: The specificity and PPV were calculated for all characteristics and for each reader. The average specificities of the three readers for the most frequently used six characteristics were as follows: spiculation, 97%+/-5 (standard deviation); taller than wide, 91%+/-4; central shadowing, 77%+/-1; markedly hypoechoic, 86%+/-5; duct extension, 95%+/-5; and microlobulation, 84%+/-3 (overall average specificity, 88.5%). The average PPVs for categories II-V were 5%, 10%, 63%, and 94%, respectively. The readers' interpretations were similar and correlated well. CONCLUSION: The proposed US recommendation system is an accurate predictor of histologic findings. A sonographic classification lexicon should prove valuable.

Breast↗

PubMed2001

Renal blood flow changes induced with endothelin-1 and fenoldopam mesylate at quantitative Doppler US: initial results in a canine study.

PURPOSE: To evaluate quantitative Doppler ultrasonography (US) for assessing renal blood flow changes induced with endothelin-1 (ET-1) and fenoldopam mesylate in conscious dogs. MATERIALS AND METHODS: A blood flow probe was surgically implanted around the renal artery in eight adult dogs. Color and power Doppler US images were acquired in conscious restrained dogs during intravenous infusion of ET-1 and fenoldopam mesylate. Simultaneous with imaging, blood flow through the renal artery was measured with the implanted probe. The color level of the images within the region representing the kidney was analyzed to derive flow indices. These indices were compared with direct-flow measurements. RESULTS: The flow indices, color-weighted flow area (CWFA), and percentage of area of color, derived from color and power Doppler US images, correlated linearly with direct flow. The mean color level of color and power Doppler US images correlated weakly with direct flow. Pre- versus postinfusion CWFA decreased with all ET-1 infusions (P < or =.032). Infusion of fenoldopam mesylate increased CWFA in all cases (P < or =.032). CONCLUSION: Quantitative Doppler US enabled successful measurement of the flow changes induced with ET-1 and fenoldopam mesylate. Quantitative Doppler US is potentially useful as a noninvasive surrogate endpoint in evaluating the action of various therapeutic agents.

Animals↗

PubMed2001

Use of quantitative analysis of sonographic brightness for detection of early healing of tendon injury in horses.

OBJECTIVES: To determine whether quantitative analysis of sonographic brightness could be used to detect healing of an induced injury of the superficial digital flexor tendon in horses and whether rate of healing was influenced by equine recombinant growth hormone. ANIMALS: 8 clinically normal Standardbreds. PROCEDURES: A localized injury was created in the left and right superficial digital flexor tendons of each horse by injection of 2,000 units of collagenase. After injury, 4 horses received equine recombinant growth hormone, a possible promoter of tendon healing. Sonographic images (7.5 MHz) of the flexor tendons and ligaments of the metacarpal region were recorded on videotape prior to injury and weekly for 7 weeks after injury. Images were digitized, and sonographic brightness of tendons and ligaments was calculated. RESULTS: Collagenase-induced injury was sonographically similar to naturally occurring injury. After injury, sonographic brightness of the tendon decreased; after 3 weeks, brightness progressively increased, although by 7 weeks brightness had not returned to preinjury value. Equine recombinant growth hormone had no significant effect on the rate of tendon healing, as evaluated sonographically or at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: As healing developed, alterations in sonographic brightness of injured tendons coincided with real changes in tendon structure. Quantitative sonographic brightness could be used to accurately monitor healing of equine tendon and ligament injuries and investigate the efficacy of various treatment regimens.

Animals↗

PubMed2000

Quantitative vascularity of breast masses by Doppler imaging: regional variations and diagnostic implications.

Seventy-four biopsy proven breast masses were imaged by color and power Doppler imaging to evaluate vascular pattern of malignant and benign breast masses. The images were analyzed for vascularity. The measurements were made over the entire mass as well as regionally at its core, at its periphery, and in the tissue surrounding it. The surgical specimens were analyzed for microvessel density. The diagnostic performance of Doppler sonographic vascularity indices was evaluated by receiver operating characteristic analysis. The malignant masses were 14 to 54% more vascular than the benign masses. Both types of masses were more vascular by ultrasonography than the tissue surrounding them. Whereas benign masses were 2.2 times more vascular than the surrounding tissue, the malignant masses were 5.0 times more vascular. In a subset of patients the regional vascularity at the core, periphery, and surrounding tissue by Doppler imaging exhibited a strong correlation (R2 > 0.9) with the corresponding histologic microvessel density measurements. Although the malignant masses exhibited a strong gradient in vascularity, core > periphery > surrounding tissue, the benign masses had relatively uniform distribution of vascularity. The area under the receiver operating characteristic curve (A(Z)) for the Doppler indices ranged from 0.56 +/- 0.07 to 0.65 +/- 0.07. A nonlinear analysis including age-specific values of Doppler indices improved the diagnostic performance to A(Z) = 0.85 +/- 0.06. In conclusion, quantitative Doppler imaging when used in combination with a nonlinear rule-based approach has the potential for differentiating between malignant and benign masses.

Adult↗

PubMed2000

Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication.

Prostacyclin is an endothelially derived vasodilator and inhibitor of platelet aggregation. Despite its therapeutic potential for peripheral arterial disease, the short half-life and chemical instability are barriers to routine therapy. Accordingly, prostacyclin analogs are being evaluated in patients with peripheral arterial disease. State-of-the-art non-invasive ultrasonography allows for serial testing of the hemodynamic effects of vasoactive drugs. The safety, efficacy and hemodynamic effects of UT-15, a novel, long-acting prostacyclin analog, were studied in patients with severe intermittent claudication. A total of eight patients with stable severe intermittent claudication, Fontaine classes IIb-III, were admitted to the hospital for intravenous infusion of UT-15. A symptom-limited, dose-escalation protocol was instituted, beginning with placebo and then with increasing dosage at 60-min intervals, followed by a 2-h period of maintenance dose at the maximum well-tolerated infusion rate. The hemodynamic response in the lower limbs was assessed with serial ultrasonography, segmental arterial pressures and pulse volumes. Blood flow in the common femoral artery increased 29% (p = 0.003) by the end of the maintenance period and remained above baseline throughout the washout period (p = 0.044). Blood velocity in the lower limb increased in most of the peripheral arteries. These increases achieved statistical significance in the common femoral artery (p = 0.025) and anterior tibial artery (p = 0.019), and approached significance in the popliteal artery (p = 0.062). In two of four patients in whom blood flow was undetectable before the infusion, arterial blood flow at the ankle level became apparent on ultrasonography during maintenance infusion. UT-15 infusion improved the pulse volume recording (p = 0.016) but the ankle/brachial index did not change significantly. Common side effects at peak dose included headache and nausea. There were no serious adverse events attributable to UT-15 treatment. In most patients, the optimal infusion rate was 10-20 ng/kg per min. In conclusion, ultrasonography is a novel approach for assessing the hemodynamic response to vasoactive agents. UT-15 is well tolerated when given for up to 2 h and increases arterial blood flow and velocity in patients with severe intermittent claudication.

Aged↗

PubMed1999

Evaluation of change in blood flow by contrast-enhanced power Doppler imaging during norepinephrine-induced renal vasoconstriction.

We evaluated the changes in flow induced by intrarenal infusion of norepinephrine by an ultrasonographic contrast agent and power Doppler imaging. Hypoperfusion was induced in dogs (N = 5) by infusing norepinephrine directly into the renal artery for 30 min at doses of 0.7 microg/kg/min, 1.0 microg/kg/min, and 1.9 microg/kg/min. Contrast agent injections were made before and after each infusion of norepinephrine. The transit of contrast agent through the kidney and color enhancement were measured by computer analysis of power Doppler images. Mean transit time and effective renal plasma flow were measured. The effective renal plasma flow decreased by 29%, 30%, and 64%, respectively, with the increasing doses of norepinephrine. Paralleling this change, the mean transit time, which corresponds to reduction in renal blood flow, increased by 26%, 43%, and 77%, respectively, from the preinfusion value. Regression analysis shows renal blood flow to decrease exponentially with norepinephrine dose. Renal blood flow changes measured by contrast-enhanced imaging correlated closely with the effective renal plasma flow measurements. Computer analysis of contrast-enhanced power Doppler images allowed measurement of renal blood flow. This technique may be useful in assessing renal perfusion during pharmacologic and other therapeutic interventional procedures.

Animals↗

PubMed1998

Comparison of power Doppler and B-scan sonography for renal imaging using a sonographic contrast agent.

The goal of this study was to evaluate the relative performance of power Doppler and B-scan imaging modes in detecting vascular perfusion changes resulting from injection of a contrast agent. To allow this comparison the imaging plane and the contrast agent injection must be the same for both modes. We achieved this by using a rigid transducer holder and simultaneously recording power Doppler and B-scan images on separate videotapes. The kidneys of five adult beagles were scanned to allow a comparison of how power Doppler and B-scan imaging methods monitor changes during the injection of 0.1 ml/kg of a contrast agent, EchoGen emulsion (Sonus Pharmaceuticals, Bothell, WA). The changes in the images were assessed qualitatively by three radiologists and quantitatively using a custom-designed image analysis software. All of the radiologists agreed that no visually detectable changes occurred in B-scan images but that significant changes could be observed in power Doppler images. Image analysis also indicated a difference between power Doppler and B-scan images. The change in mean color level of power Doppler images could be displayed as an indicator dilution curve with a peak enhancement of 46 +/- 16 above the preinjection value. The time at which mean color level peaked was 18 +/- 13 s. The mean color level returned to half of the peak value by 69 +/- 42 s and returned to the preinjection baseline value by 148 +/- 73 s. Conversely, B-scan images showed statistically insignificant changes, and time measurements could not be made. By all measures used to evaluate images, power Doppler imaging had a greater sensitivity in detecting changes resulting from contrast agent injection than B-scan imaging. This finding indicates that power Doppler imaging of contrast agent injections can be used to map regional differences in flow as well as quantitative measurements of a contrast agent's transit time and has the potential to assess kidney abnormalities associated with renal blood flow.

Animals↗

PubMed1997

Use of power Doppler ultrasound-guided biopsies to locate regions of tumour hypoxia.

The purpose of this study was to determine whether power Doppler ultrasound techniques could be used to direct biopsies into tumour regions with relatively low red blood cell flux, and therefore preferentially sample regions that were relatively hypoxic. Subcutaneous 9L glioma rat tumours were biopsied using power Doppler ultrasound guidance. Immunohistochemical detection of the 2-nitroimidazole EF5 was performed to determine the presence and level of hypoxia in the biopsy samples. Comparisons between the power Doppler-determined red blood cell flux and EF5 binding were made. In seven out of eight tumours studied, power Doppler ultrasound allowed differentiation of a relatively hypoxic region from a relatively oxic region by localizing relatively low vs high red blood cell flux areas respectively. In one of these seven tumours, RBC flux was high in both biopsied sites and hypoxia was not present in either. In two of these seven tumours, hypoxia was present in each biopsy and both of the red blood cell flux measurements were low. In the eighth tumour, both the EF5 binding and the red blood cell flux measurements were low. In this tumour, low EF5 binding was due to the dominance of necrotic cells, which will not reduce or bind EF5 in the biopsy specimen. Using EF5-binding techniques, we have confirmed that regions of relatively low red blood cell flux are more hypoxic than those with relatively high red blood cell flux. Counterstaining specimens with haematoxylin and eosin allows differentiation of low EF5-binding regions due to oxia vs necrosis. These methods have clinical implications for the expanded use of power Doppler ultrasound as a means to direct tissue sampling when it is important to identify the presence of hypoxia.

Animals↗

PubMed1997

Mathematical modeling of the dilution curves for ultrasonographic contrast agents.

Most techniques using sonographic contrast agents are based on introducing the agent intravenously. The sonographic changes occur over time and follow a characteristic "skewed gaussian curve," often referred to as the indicator dilution curve. This study uses principles of linear acoustics and tracer kinetics to develop a quantitative model for the indicator dilution curve. A rapid increase in image brightness occurs after bolus injection; brightness peaks after a time related to the blood flow and stability of the contrast agent, which is followed by an asymptotic decrease in image brightness. The net image enhancement, represented by the area under the dilution curve, increases nonlinearly with the injected dose. In stable contrast agents the peak-time and mean transit time are related directly to the flow rate. This relationship changes when the microbubbles of a contrast agent collapse. In an unstable contrast agent the indicator dilution curve is attenuated and peaks earlier than expected on the basis of flow rate. The extent of shift in the mean transit time varies with the half-life of the contrast agent and follows a sigmoid relationship. In conclusion, the properties of the time-videointensity (indicator dilution) curves are significantly affected by the attenuation and stability of the contrast agents. These factors must be taken into consideration in deriving flow related information.

Absorption↗

PubMed1996

Power, spectral, and color flow Doppler enhancement by a new ultrasonographic contrast agent.

The ability of EchoGen contrast agent (Sonus Pharmaceuticals, Bothell, WA) to enhance aortic, renal, and scrotal spectral Doppler, color flow, and power Doppler sonography at doses from 0.01 ml/kg to 0.65 ml/kg was evaluated in dogs. Videotaped images were digitized and analyzed for Doppler signal strength at known postinjection times. Contrast agent increased aortic spectral Doppler peak height, spectral width, and brightness. Contrast agent increased renal and testicular color flow and power Doppler sonographic signal and enhanced the visualization of vascular anatomy. Intensity and duration of these effects increased with increasing dose of contrast agent. Enhancement effect varied in different organs. At higher doses, blooming and Doppler shift artifacts were observed and are believed to be due to machine limitation.

Animals↗

PubMed1995

Quantitation of organ symmetry by diagnostic ultrasonic imaging: a group theoretical approach.

A method based on group theory is proposed to quantify the shape of an organ. It is proposed that a complex shape is characterized by a basic set of symmetry operations involving rotation about the center axis. Based on this concept, partial symmetry elements (PSE) were determined by stepwise rotation of the images and measurement of overlap area between the original and rotated images. These measurements were used to define a symmetry index (SI) and to "decompose" the complex shape into simpler shapes with regular geometry such as a circle, an ellipse, an equilateral triangle, a square, etc. Computer simulations and two-dimensional (2-D) ultrasonic images of the prostate were used to demonstrate the feasibility of the method. The method was also applied to a series of clinical ultrasonic cardiac images to determine the dynamic shape changes in left ventricle (LV) of a normal heart and an heart with infarction. The results of this study show that SI increased with an increase in the symmetry of the simulation models and the prostate. Cross-sectional images of prostate with triangular and ellipsoidal shapes exhibited larger proportion of three-fold and two-fold symmetries, respectively. Symmetry index of the LV changed during the cardiac cycle and exhibited a loop-like structure when plotted as a function of size. Quantitative measurements of SI indicated that the left ventricular chamber is rounder during the diastolic phase of the cardiac cycle. The loop-like structure was considerably reduced in the heart with infarction. Also, larger distortions in cardiac shape were observed over cardiac cycle in the heart with infarction, as compared to the normal heart. In conclusion, it is feasible to quantitatively characterize 2-D shapes of the organs by symmetry operations based on group theoretical analysis.

Diagnosis, Computer-Assisted↗

PubMed1995

Influence of postprocessing curves on contrast-echographic imaging: preliminary studies.

The aim of this study was to evaluate the influence of postprocessing curves on the visual and quantitative enhancement of image brightness caused by the injection of a contrast agent. A fixed dose (0.45 ml/kg) of contrast agent EchoGen was injected into three dogs, and images of the kidney were investigated using one linear (A) and three nonlinear (B, C, D) postprocessing curves. Curve D gave the best gray scale images and was generally used for diagnostic imaging. Images were analyzed qualitatively in three dogs and quantitatively in one dog for brightness change caused by contrast agent injection. Visually the changes were most identifiable with curve C and least by curve D. Video intensity time curves reflected the qualitative changes. Peak contrast and area under the video density curve changed in the order curve D < curve B approximately curve A < curve C. Choice of the postprocessing curve can have a marked influence on the enhancement of image brightness by a contrast agent. Postprocessing curves optimized to display a wide range of echo levels may not always be an ideal choice for contrast sonography.

Animals↗

PubMed1995

Sonographic enhancement of renal cortex by contrast media.

The purpose of this study was to evaluate whether a phase shift contrast agent could enhance the renal cortex. Four doses of the contrast agent EchoGen ranging from 0.25 to 0.65 ml/kg were injected intravenously in three healthy dogs. Images of the kidney were recorded on a videotape before and after each injection. The images were evaluated visually and were computer-analyzed for brightness change caused by the contrast agent. Marked changes in cortical brightness were observed at the doses of 0.45 and 0.65 ml/kg. At lower doses the changes in image brightness were significantly reduced but measurable. The brightness peaked at 65 +/- 9 seconds after injection and gradually decreased to the baseline value in approximately 12 minutes. The video density varied nonlinearly with dose, and at low doses its value drifted below the baseline. This is believed to be due to attenuation of echoes by the contrast agent. The results of this study indicate that the microbubbles formed by phase shift contrast media are sufficiently small and persist long enough to enhance sonographic images of the cortex. Contrast media whose effect is based on the phenomenon of phase shift permit enhancement of the gray scale characteristic of the kidney. The enhancements last up to several minutes and have strong potential to allow investigation of perfusion in kidney.

Animals↗

PubMed1994

Three-dimensional US and volumetric assessment of the prostate.

The authors demonstrate a method for constructing three-dimensional (3D) images of the prostate based on standard two-dimensional ultrasonic (US) images. Transverse US images of the prostate in six patients (aged 61-83 years) and 10 water-filled balloon phantoms were recorded at video rates by manually withdrawing a biplane transrectal probe at a constant speed. Data acquisition time of the images was less than a minute. Typically, 50-70 scans of 0.2-0.5-mm-thick cross sections were acquired. Postprocessing of these data enabled lifelike 3D visualization of the gland and accurate measurement of its volume.

Aged↗

PubMed1994

Three-dimensional volumetric ultrasound imaging of arterial pathology from two-dimensional intravascular ultrasound: an in vitro study.

The objectives of this study were to evaluate: (1) the feasibility of generating three-dimensional (3-D) ultrasound (US) volumetric images of arterial segments from intravascular (IV) US images by retaining full range of gray levels; (2) the feasibility of volumetric quantitation of various arterial wall pathology from the 3-D volume US images of arterial segments. IVUS provides morphologic details of arterial wall diseases. This is seen as variation in gray levels. However, when a 3-D US image is generated currently, the full range of gray levels is not utilized. This limits optimal assessment of arterial wall pathology. Sequential cross-sectional IVUS images from 11 arterial segments consisting of various pathology were obtained in vitro by calibrated withdrawal of an IVUS catheter. These images were digitized by an 8 bit digitizer to retain full 256 gray levels of brightness. 3-D volume generation was carried out using "ANALYZE" software. After the IVUS imaging, arterial segments were sectioned transversely in a 0.3-0.4 mm cross section and stained with hematoxylin, eosin and elastin. Geometrical measurements and gross morphological changes of the arterial segments were noted and correlated with the corresponding section of the image from the three-dimensional volume. Arterial wall pathology, its extent and its effect on lumen geometry were easily appreciated in multiple tomographic sections of a 3-D volume image. Similarly, arterial wall pathology was easily quantitated from 3-D volume. The above assessments were only feasible by retaining full range of gray levels in the 3-D volume image. This study indicates that (1) it is feasible to generate a 3-D US volume image by retaining full range of gray levels from IVUS images, (2) retaining full range of gray levels allows optimal assessment of arterial wall pathology and its extent in 3-D volume, and (3) IVUS allows quantitation of arterial wall pathology, and thereby one can assess the effect of intervention.

Arteries↗