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Biomedical subjects

S Molloi

Publications and source records attributed to S Molloi.

At least 19 recordsLinked to original sources

Analysis of blood flow in the entire coronary arterial tree.

A hemodynamic analysis of coronary blood flow must be based on the measured branching pattern and vascular geometry of the coronary vasculature. We recently developed a computer reconstruction of the entire coronary arterial tree of the porcine heart based on previously measured morphometric data. In the present study, we carried out an analysis of blood flow distribution through a network of millions of vessels that includes the entire coronary arterial tree down to the first capillary branch. The pressure and flow are computed throughout the coronary arterial tree based on conservation of mass and momentum and appropriate pressure boundary conditions. We found a power law relationship between the diameter and flow of each vessel branch. The exponent is approximately 2.2, which deviates from Murray's prediction of 3.0. Furthermore, we found the total arterial equivalent resistance to be 0.93, 0.77, and 1.28 mmHg.ml(-1).s(-1).g(-1) for the right coronary artery, left anterior descending coronary artery, and left circumflex artery, respectively. The significance of the present study is that it yields a predictive model that incorporates some of the factors controlling coronary blood flow. The model of normal hearts will serve as a physiological reference state. Pathological states can then be studied in relation to changes in model parameters that alter coronary perfusion.

Animals↗

A computer reconstruction of the entire coronary arterial tree based on detailed morphometric data.

A rigorous analysis of blood flow must be based on the branching pattern and vascular geometry of the full vascular circuit of interest. It is experimentally difficult to reconstruct the entire vascular circuit of any organ because of the enormity of the vessels. The objective of the present study was to develop a novel method for the reconstruction of the full coronary vascular tree from partial measurements. Our method includes the use of data on those parts of the tree that are measured to extrapolate the data on those parts that are missing. Specifically, a two-step approach was employed in the reconstruction of the entire coronary arterial tree down to the capillary level. Vessels > 40 microm were reconstructed from cast data while vessels < 40 microm were reconstructed from histological data. The cast data were reconstructed one-bifurcation at a time while histological data were reconstructed one-sub-tree at a time by "cutting" and "pasting" of data from measured to missing vessels. The reconstruction algorithm yielded a full arterial tree down to the first capillary bifurcation with 1.9, 2.04 and 1.15 million vessel segments for the right coronary artery (RCA), left anterior descending (LAD) and left circumflex (LCx) trees, respectively. The node-to-node connectivity along with the diameter and length of every vessel segment was determined. Once the full tree was reconstructed, we automated the assignment of order numbers, according to the diameter-defined Strahler system, to every vessel segment in the tree. Consequently, the diameters, lengths, number of vessels, segments-per-element ratio, connectivity and longitudinal matrices were determined for every order number. The present model establishes a morphological foundation for future analysis of blood flow in the coronary circulation.

Algorithms↗

Neoplastic transformation in vitro after exposure to low doses of mammographic-energy X rays: quantitative and mechanistic aspects.

The induction of neoplastic transformation in vitro after exposure of HeLa x skin fibroblast hybrid cells to low doses of mammography-energy (28 kVp) X rays has been studied. The data indicate no evidence of an increase in transformation frequency over the range 0.05 to 22 cGy, and doses in the range 0.05 to 1.1 cGy may result in suppression of transformation frequencies to levels below that seen spontaneously. This finding is not consistent with a linear, no-threshold dose- response curve. The dose range at which possible suppression is evident includes doses typically experienced in mammographic examination of the human breast. Experiments are described that attempt to elucidate any possible role of bystander effects in modulating this low-dose radiation response. Not unexpectedly, inhibition of gap junction intercellular communication (GJIC) with the inhibitor lindane did not result in any significant alteration of transformation frequencies seen at doses of 0.27 or 5.4 cGy in these subconfluent cultures. Furthermore, no evidence of a bystander effect associated with factors secreted into the extracellular medium was seen in medium transfer experiments. Thus, in this system and under the experimental conditions used, bystander effects would not appear to be playing a major role in modulating the shape of the dose-response curve.

Bystander Effect↗

Mechanisms of suppression of neoplastic transformation in vitro by low doses of low LET radiation.

Suppression of neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro following low doses of low linear energy transfer radiation has been reported previously. The present study represents an exploration of two hypothesized mechanisms that may underlie this observed suppression. These are the up-regulation of reduced glutathione (GSH), a known antioxidant, and induction of DNA repair activity. The hybrid cells were found to have a high endogenous level of GSH and no induction following low doses of 60 kVp X-rays was observed. Buthionine sulfoximine (BSO), a GSH biosynthesis inhibitor, completely suppressed GSH levels in both unirradiated and irradiated cells. Furthermore, there was no significant impact of BSO-induced suppression of GSH on the neoplastic transformation frequency of either unirradiated or low dose irradiated cells indicating that glutathione levels play no role in the low dose suppression of transformation frequency. To assess the possible role of DNA repair in the low dose suppression of transformation the effect of 3-aminobenzamide (3-AB), a poly-ADP-ribose polymerase (PARP) inhibitor was examined. In these experiments, there was no significant effect of 3-AB on the transformation frequency at a dose of Cs-137 gamma rays of 0.5 cGy, however, at a dose of 5 cGy there was a significant increase (P < 0.05) in the transformation frequency in the presence of 3-AB. These findings suggest that the influence of DNA repair on the low dose suppression of transformation is significant at a dose of 5 cGy, but not at the lower dose of 0.5 cGy.

Antioxidants↗

Low doses of diagnostic energy X-rays protect against neoplastic transformation in vitro.

PURPOSE: To investigate the effect of low doses of 60 kVp X-rays on in vitro transformation frequency. MATERIALS AND METHODS: HeLa x skin fibroblast human hybrid cells were used to assay transformation from the non-tumorigenic to the tumorigenic phenotype. Subconfluent cultures of cells were exposed to a range of doses of 60 kVp X-rays and seeded for assay of transformation after 24 h post-irradiation holding. Experiments were repeated at least three times and the data pooled for analysis. Transformation frequencies were compared with those of sham-irradiated controls. RESULTS: At doses < 1 cGy, the observed transformation frequencies were significantly less than those seen in unirradiated cells. CONCLUSION: Low doses (< 1 cGy) of 60 kVp X-rays protect HeLa x skin fibroblast human hybrid cells against neoplastic transformation in vitro.

Cell Transformation, Neoplastic↗

Quantification of coronary artery lumen volume by digital angiography: in vivo validation.

BACKGROUND: Coronary artery lumen volume may potentially have several advantages over the commonly used variables, such as percent stenosis or minimal lumen diameter, in the assessment of coronary artery disease. The goal of this study is to validate a quantitative assessment of lumen volume using a video densitometry technique. METHODS AND RESULTS: Coronary arteriography was performed in 9 swine (body weight 20 to 55 kg) after power injection of contrast material (2 mL/s for 3 seconds) into the left main coronary artery. Phase-matched subtracted images were used to quantify regional lumen volume by a video densitometry technique. The in vivo volume measurements were validated by a polymer cast of the coronary arterial tree made at physiological pressure. The measured cast volume (V(C)) and video densitometric regional lumen volume (V(VD)) were related by V(VD)=1.06 V(C)-0.01 mL (r=0.99). The root mean square and systematic errors for these measurements were 17% and -3%, respectively. CONCLUSIONS: A video densitometry technique for quantification of coronary lumen volume was validated both in vitro and in vivo in a swine animal model. The present results demonstrated the feasibility and potential utility of the video densitometry technique for accurate measurement of regional lumen volume in vivo. This study contributes to the understanding of the angiographic methods used for the assessment of coronary artery disease and indicates that this technique can potentially be used for quantification of diffuse coronary artery disease during routine coronary arteriography.

Angiography, Digital Subtraction↗

X-ray beam equalization: feasibility and performance of an automated prototype system in a phantom and swine.

PURPOSE: To investigate the feasibility of an automated implementation of a beam equalization technique and to evaluate the experimental performance of the prototype system. MATERIALS AND METHODS: X-ray beam equalization involved the process of low-dose image acquisition, attenuator thickness calculation, mask generation, mask positioning, equalized image acquisition, and mask reshaping. The entire equalization process was performed in approximately 7 seconds. The equalized images were assessed both qualitatively and quantitatively by using a humanoid phantom and a swine animal model. The general image quality was assessed for the ability to visualize arterial branches and other anatomic structures. The level of equalization was quantitatively assessed by segmenting the images into an 8 x 8 matrix of square regions. RESULTS: The ratio of the root-mean-squared variance for the equalized and unequalized images from humanoid phantom and swine animal studies was 0.49 and 0.59, respectively. Furthermore, qualitative assessment of the images showed substantial improvement in image quality and visualization of arterial branches after beam equalization in phantom and animal studies. CONCLUSION: Automated area beam equalization is feasible and improves image quality in previously underpenetrated regions of the image.

Animals↗

Cross-sectional area and volume compliance of porcine left coronary arteries.

We have determined the cross-sectional area (CSA) compliance of the first several generations of pig coronary arteries and the volume compliance of the coronary arterial tree (vessels >0.5 mm in diameter) using a videodensitometric technique. The coronary arteries of four KCl-arrested maximally vasodilated pig hearts were perfused with iodine and 3% Cab-O-Sil. Because Cab-O-Sil occludes small arteries, the flow can be stopped and the pressure can be maintained while the trunk of the coronary artery and its subbranches are imaged using digital angiography. The coronary arteries were preconditioned several times with cyclic changes in pressure from 0 to 160 mmHg. The pressure was then varied in a triangular pattern, and the absolute CSA of each vessel and the total arterial volume were calculated using videodensitometry in conjunction with digital subtraction angiography. Our results have shown that the pressure-diameter and pressure-volume relationships are linear in the 60-140 mmHg pressure range. Furthermore, the compliance of the coronary arteries is small; i.e., the diameter of the coronary artery changes by <15% in the 80-mmHg pressure range. The compliance data couples the mechanics of the blood vessel wall to the mechanics of blood flow to yield a pressure-flow relationship for each coronary arterial segment.

Animals↗

On the design of the coronary arterial tree: a generalization of Murray's law.

Murray's law has been generalized to provide morphometric relationships among various subtrees as well as between a feeding segment and the subtree it perfuses. The equivalent resistance of each subtree is empirically determined to be proportional to the cube of a subtree's cumulative arterial length (L) and inversely proportional to a subtree's arterial volume (V) raised to a power of approximately 2.6. This relationship, along with a minimization of a cost function, and a linearity assumption between flow and cumulative arterial length, provides a power law relationship between V and L. These results, in conjunction with conservation of energy, yield relationships between the diameter of a segment and the length of its distal subtree. The relationships were tested based on a complete set of anatomical data of the coronary arterial trees using two models. The first model, called the truncated tree model, is an actual reconstruction of the coronary arterial tree down to 500 microm in diameter. The second model, called the symmetric tree model, satisfies all mean anatomical data down to the capillary vessels. Our results show very good agreement between the theoretical formulation and the measured anatomical data, which may provide insight into the design of the coronary arterial tree. Furthermore, the established relationships between the various morphometric parameters of the truncated tree model may provide a basis for assessing the extent of diffuse coronary artery disease.

Arteries↗

Scatter and veiling glare estimation based on sampled primary intensity.

Scatter and veiling glare are predominant sources of error in videodensitometric iodine quantification. Standard beam stop techniques such as lead strips or an array of lead discs, placed before the patients, have previously been used to measure scatter and veiling glare in digital radiographic images. However, these techniques significantly increase patient x-ray exposure. In order to overcome this limitation, a scatter measurement technique based on sampled primary intensity has been investigated. This technique uses an array of apertures in a lead sheet to sample the primary x-ray intensity. The scatter-glare intensity in these locations is calculated by subtracting the sampled primary intensity from an open field image which contains both primary and scatter-glare. The calculated scatter-glare values can be interpolated or combined with digital filtration to estimate the scatter-glare intensity on a pixel by pixel basis. The technique was evaluated using a Lucite step phantom and an anthropomorphic chest phantom. The average rms percentage errors of scatter and veiling glare estimation using bi-cubic interpolation and digital filtration techniques were 8.02% and 7.53%, respectively. The average rms percentage errors of primary intensity estimation using bi-cubic interpolation and digital filtration techniques were 10.01% and 8.91%, respectively. The x-ray exposure-area product (EAP) from the aperture array was only 4.38% of the EAP from the open field. These results indicate that the scatter-glare intensity can be accurately estimated with minimal x-ray exposure using sampled primary intensity.

Densitometry↗

Area x-ray beam equalization for digital angiography.

An area beam equalization technique has been investigated in order to generate patient-specific compensating filters for digital angiography. An initial image was used to generate the compensating filter, which was fabricated using a deformable compensating material, containing CeO2, and an array of square pistons. The CeO2 attenuator thicknesses were calculated using the gray level information from the initial unequalized image. The array of pistons was pressed against a uniform thickness of attenuating material to generate a filter for x-ray beam equalization. The filter was subsequently inserted into the x-ray beam for the final equalized radiograph. It was positioned close to the focal spot (magnification of 8.0) in order to minimize edge artifacts from the filter. The equalization of x-ray transmission across the field exiting from the object significantly improved the image quality by preserving local contrast throughout the image. The contrast-to-noise ratio (CNR) in the equalized images was increased-by up to fivefold. Phantom studies indicate that equalized images using a relatively small array of pistons (e.g., 8 x 8) produce significant improvement in image quality with negligible perceptible artifacts. Animal studies showed that beam equalization significantly improved fluoroscopic and angiographic image quality. X-ray beam equalization produced an image with a relatively uniform scatter-glare intensity and it reduced the scatter-glare fraction in the previously underpenetrated region of the image from 0.65 to 0.50. Also, x-ray tube loading due to the mask assembly itself was negligible. In conclusion, area beam equalization reduces the scatter-glare fraction and significantly improves CNR in the previously underpenetrated region of the image.

Angiography, Digital Subtraction↗

Absolute volumetric coronary blood flow measurement with digital subtraction angiography.

The problems associated with visual interpretation of coronary arteriograms have been well-documented. There is a need for more physiologic means of assessing coronary artery stenosis during routine coronary arteriography. Volumetric coronary blood flow assessed as a function of time can be a valuable aid in the analysis of functional significance of arterial obstruction. A volumetric coronary blood flow measurement technique was investigated in a swine animal model using phase matched temporal subtraction images. The left anterior descending (LAD) coronary artery of swine animal models were instrumented with an ultrasound flow probe (US) and a vascular occluder producing stenosis. Contrast material injections (2-4 ml/sec for 3 sec) were made into the left coronary ostium during image acquisition. Phase-matched temporal subtraction (DSA) images were used to measure volumetric coronary blood flow in the LAD. In addition, a technique for automatic estimation of iodine calibration slope was also investigated. In 49 independent comparisons, the mean coronary blood flow (FPA) correlated extremely well with the mean US flow (FPA = 0.92US + 1.42 ml/min, r = 0.99, standard error of estimate (SEE) = 4.32 ml/min). Further more, the automatic iodine calibration technique was shown to be very accurate. In conclusion, accurate volumetric coronary blood flow measurements can be made before the onset of significant changes in coronary blood flow due to contrast injection.

Angiography, Digital Subtraction↗

Scatter-glare estimation for digital radiographic systems: comparison of digital filtration and sampling techniques.

The scatter and veiling glare distribution in images acquired with a digital subtraction angiography imaging system was estimated using a digital filtration and a beam-stop technique. The digital filtration technique utilizes exposure parameters and image gray levels to estimate scatter-glare intensity based on previous phantom measurements. The beam-stop technique uses an array of lead discs in order to sample scatter-glare intensity for each patient. To test the ability of digital filtration and beam-stop techniques to estimate the scatter-glare intensity, they were applied to images of postmortem swine animal models at different projections and beam energies. The systematic and root-mean-square (rms) percentage errors of these estimates were obtained by comparison to directly measured scatter-glare images using a scanning lead strip technique. The average rms percentage error for the digital filtration and beam-stop techniques were 8.07% and 6.67%, respectively. The changes in scatter-glare intensity due to contrast injection during coronary arteriography and ventriculography were also measured using the beam-stop technique. The maximum changes in scatter-glare intensities during coronary arteriography and ventriculography were 19 and 88%, respectively. The results indicate that the digital filtration technique is more suited for applications such as coronary arteriography and ventriculography where the iodinated contrast material significantly changes the scatter-glare intensity.

Angiography, Digital Subtraction↗

Measurement of a cross-sectional area of normal and stenotic arteries with videodensitometric quantitative arteriography and intravascular ultrasound.

RATIONALE AND OBJECTIVES: A videodensitometric technique that allows measurement of absolute cross-sectional area of any complex lesion was compared with an intravascular ultrasound (US) technique. METHODS: Stenotic devices (10-15 mm long) with cross sections of different shapes were placed in the distal aortas of five anesthetized pigs (weight, 40-50 kg). The stenotic devices were imaged by using an intravascular US probe after power injection of contrast material. RESULTS: A comparison of actual areas and measured cross-sectional areas of the stenotic devices showed that videodensitometry and intravascular US produced better results than edge-detection techniques for both unsubtracted and temporal subtraction images. CONCLUSION: These data suggest that the videodensitometric technique can be used to measure absolute cross-sectional areas of arteries with different shapes.

Absorptiometry, Photon↗

Quantification of volumetric coronary blood flow with dual-energy digital subtraction angiography.

BACKGROUND: As a solution to the well-documented problems associated with visual interpretation of coronary arteriograms, more physiological methods of assessing coronary artery stenosis are being investigated. Volumetric coronary blood flow (BF) can be a valuable aid in the analysis of functional significance of arterial obstruction. METHODS AND RESULTS: The left anterior descending coronary artery (LAD) of 15 anesthetized pigs (40 to 50 kg) was dissected free from the epicardium in its proximal portion, and a transmit-time ultrasound flow probe of the appropriate size was applied. A vascular occluder was positioned distal to the flow probe for flow adjustments. Contrast injections (2 to 4 mL/s for 3 seconds) were made into the left main coronary artery during image acquisition with a motion-immune dual-energy digital subtraction angiography (DE DSA) system. Tissue-suppressed energy-subtracted images were used to generate time-density curves. BF measurements were made in the LAD vascular bed with use of the time-density curve, with consideration that blood was momentarily replaced with contrast during the injection. In 19 comparisons, the mean BF, measured with the use of DE DSA, correlated extremely well with the mean ultrasound flow (DE DSA=0.90 ultrasound+3.10 mL/min, r=.96). Also, contrast injection increased the BF by an average of only 15% during the image-acquisition time interval. CONCLUSIONS: Accurate BF measurements can be made with motion-immune DE DSA. The BF measurements can be completed before the onset of significant changes in BF due to contrast injection. Furthermore, it is possible to make the BF measurements during routine coronary arteriography.

Angiography, Digital Subtraction↗

The mechanism of cardiac shunting in reptiles: a new synthesis.

The mechanism of cardiac shunting in reptiles is controversial. Recent evidence suggests that a right-to-left shunt in turtles results primarily from a washout mechanism. The mechanism that accounts for left-to-right (L-R) shunting is unresolved. This study used haemodynamic analysis and digital subtraction angiography to determine the mechanism of L-R cardiac shunting in the turtle Trachemys (Pseudemys) scripta. Animals were instrumented with ultrasonic blood flow probes (Transonic Systems, Inc.) for the measurement of total pulmonary blood flow and total systemic blood flow. In addition, catheters were inserted into the common pulmonary artery (PA), the systemic arteries, the left atrium and right atrium. These catheters were used for the measurement of blood pressure or for the infusion of radio-opaque material. Haemodynamic conditions were altered by electrical stimulation of the afferent (VAF) or efferent vagal nerves or by infusion of vasoactive drugs. Under control conditions, the peak systolic pressure in the systemic arteries was slightly higher than that in the PA (30.6 versus 28.3 mmHg; 4.08 versus 3.77 kPa), whereas diastolic pressure in the PA was significantly less than that in the systemic arteries (9.8 versus 24.4 mmHg; 1.31 versus 3.25 kPa). During VAF stimulation, the peak systolic pressures in the PA and aortae almost doubled. Diastolic pressure in the systemic arteries also doubled, but it increased by only 45% in the PA. Ejection of blood into the PA preceded that into the left aorta by 53 ms under control conditions. This difference increased (by as much as 200 ms) as the difference in the diastolic pressures between the two circulations increased during VAF stimulation. This resulted in the development of a large net L-R shunt. Under these conditions, digital subtraction angiography showed that the L-R shunt resulted from a combination of both washout and pressure mechanisms.

Angiography, Digital Subtraction↗

In-vivo validation of videodensitometric coronary cross-sectional area measurement using dual-energy digital subtraction angiography.

Previous studies indicate that conventional geometric edge detection techniques, used in quantitative coronary arteriography (QCA), have significant limitations in quantitating coronary cross-sectional area of small diameter (D) vessels (D < 1.00 mm) and lesions with complex cross-section. As a solution to this problem, we have previously reported on an in-vitro validation of a videodensitometric technique that quantitates the absolute cross-sectional area including small vessel diameter (D < 1.00 mm) and any complex shape of the vessel cross-section. For in-vivo validation, plastic tubing (5-8 mm long) with different shape complex cross-section with known cross-sectional area (A = 0.8-4.5 mm2) were percutaneously wedged in the coronary arteries of anesthetized pigs (40-50 kg). Contrast material injections (6-10 ml at 2-4 ml/sec) were made into the left main coronary artery during image acquisition using a motion immune dual-energy subtraction technique, where low and high X-ray energy and filtration were switched at 30 Hz. A comparison was made between the actual and measured cross-sectional area using the videodensitometry and edge detection techniques in tissue suppressed energy subtracted images. In eighteen comparisons the videodensitometry technique produced significantly improved results (slope = 0.87, intercept = 0.24 mm2, r = 0.94) when compared to the edge detection technique (slope = 0.42, intercept = 1.99 mm2, r = 0.39). Also, a cylindrical vessel phantom (D = 1.00-4.75 mm) was used to test the ability to calculate and correct for the effect of the out of plane angle of the arterial segment on the cross-sectional area estimation of the videodensitometry technique. After corrections were made for the out of plane angle using two different projections, there was a good correlation between the actual and the measured cross-sectional area using the videodensitometry technique (slope = 0.91, intercept = 0.11 mm2, r = 0.99). These data suggest that it is possible to quantitate absolute cross-sectional area without any assumption regarding the arterial shape using videodensitometry in conjunction with the motion immune dual-energy subtraction technique.

Angiography, Digital Subtraction↗

Accurate coronary calcium phosphate mass measurements from electron beam computed tomograms.

Precipitates of calcium phosphate in coronary arteries always indicate the presence of atherosclerosis. The mass of these precipitates is related to the severity of atherosclerosis. To determine the accuracy of electron beam computed tomographic (CT) mass estimates, we imaged 21 human hearts inside an anthropomorphic chest phantom using an Imatron C-100 electron beam CT scanner (Imatron, San Francisco, CA). We then incinerated the 63 imaged coronary arteries and weighed the mineral ash. We calculated the mass estimates from the images using an algorithm derived from a model that assumes simple radiographic properties of the coronary arteries. We also calculated the currently used coronary calcium score for each artery. Although both the mass estimates and the scores correlated with the actual mass of the incinerated specimens (r = .97 and r = .93), the correlation with the mass estimates was better (P = .02; William's test). The regression equation relating the actual mass to the mass estimates was y = 1.37 x + 14, indicating that the CT mass estimates consistently underestimate actual coronary calcium phosphate mass. We conclude that relative mass estimates using electron beam CT scanning are accurate and that both these and the currently employed calcium scores reflect the actual mass of precipitated calcium phosphate in diseased coronary arteries.

Algorithms↗