Sabee Molloi

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

Murrays 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 subtrees cumulative arterial length (L) and inversely proportional to a subtrees 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.

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 ×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 ×skin fibroblast human hybrid cells against neoplastic transformation in vitro.

Photon counting computed tomography: Concept and initial results

A concept of a photon counting cone beam CT is proposed. The system uses a new Multi Slit Multi Slice (MSMS) cone beam acquisition geometry utilizing a linear array photon counting detectors. The MSMS cone beam acquisition is a direct analogy of the scanning multislit acquisition used in projection x-ray imaging. This geometry provides a CT imaging with dose efficient scatter rejection and allows for using available photon counting detectors. The microchannel plate (MCP) detector is proposed as a linear array photon counting detector for MSMS cone beam CT system. Initial testing of the MCP detector for CT application was performed. The field of view of the prototype MCP detector is 60 mm. A delay line position encoding electronics was used. The electronics has a single channel input for evaluation of events from the entire detector field of view. This limits the system count rate at 2 x 10(5) count/s. The spatial resolution of this detector is 80 microm FWHM at 40 kVp and 200 microm FWHM at 90 kVp tube voltages. The detector noise in CT projections is less than 1 count/pixel for the 80 microm pixel size. The CT projections contain quantum-limited and scatter free signal. Images of a contrast phantom and a small animal were acquired at 50 kVp and 80 kVp tube voltages. The CT numbers for different contrast elements were calculated for a given x-ray spectrum and compared with experimental values. The quantum efficiency of the current detector is 56% at 90 kVp, which is suboptimal because of the large channel diameter (25 microm) of these MCPs. The MCPs with smaller channels and higher efficiencies are being tested. The quantum efficiency was measured to be 70% for a new MCP with 5 microm channel diameter. Design parameters of a clinically applicable photon counting MSMS cone beam CT for breast imaging was evaluated. System uses 20 cm field of view MCP detectors based on 5 microm channel MCPs and high count rate ASIC electronics. It was concluded that the MSMS cone beam CT with a photon counting MCP detector is feasible for volume breast imaging.

Radiation dose reduction using a CdZnTe-based computed tomography system: Comparison to flat-panel detectors

PURPOSE Although x-ray projection mammography has been very effective in early detection of breast cancer, its utility is reduced in the detection of small lesions that are occult or in dense breasts. One drawback is that the inherent superposition of parenchymal structures makes visualization of small lesions difficult. Breast computed tomography using flat-panel detectors has been developed to address this limitation by producing three-dimensional data while at the same time providing more comfort to the patients by eliminating breast compression. Flat panels are charge integrating detectors and therefore lack energy resolution capability. Recent advances in solid state semiconductor x-ray detector materials and associated electronics allow the investigation of x-ray imaging systems that use a photon counting and energy discriminating detector, which is the subject of this article. METHODS A small field-of-view computed tomography (CT) system that uses CdZnTe (CZT) photon counting detector was compared to one that uses a flat-panel detector for different imaging tasks in breast imaging. The benefits afforded by the CZT detector in the energy weighting modes were investigated. Two types of energy weighting methods were studied: Projection based and image based. Simulation and phantom studies were performed with a 2.5 cm polymethyl methacrylate (PMMA) cylinder filled with iodine and calcium contrast objects. Simulation was also performed on a 10 cm breast specimen. RESULTS The contrast-to-noise ratio improvements as compared to flat-panel detectors were 1.30 and 1.28 (projection based) and 1.35 and 1.25 (image based) for iodine over PMMA and hydroxylapatite over PMMA, respectively. Corresponding simulation values were 1.81 and 1.48 (projection based) and 1.85 and 1.48 (image based). Dose reductions using the CZT detector were 52.05% and 49.45% for iodine and hydroxyapatite imaging, respectively. Image-based weighting was also found to have the least beam hardening effect. CONCLUSIONS The results showed that a CT system using an energy resolving detector reduces the dose to the patient while maintaining image quality for various breast imaging tasks.

Automatic 3D vascular tree construction in CT angiography

This study presents an automatic method for 3D reconstruction of vascular trees using computed-tomography angiographic (CTA) images. The program starts with the CTA slices, performs a sequential procedure of 3D image formation, preprocessing, segmentation, thinning, skeleton pruning and tree construction. It ends with vascular trees along with quantitative data about the trees such as values of diameter, length and bifurcation angles. All the involved algorithms are presented with the emphasis given to the skeleton pruning and tree construction algorithms. The skeletons obtained using a 3D thinning algorithm may contain cycles, spurs, isolated sticks, and non-unit-width parts, which hinder tree construction. As a solution to this problem, a skeleton pruning and tree construction algorithm is proposed. At each stage of the automatic procedure, 3D rendering is provided for visual inspection of the computed results. In the final output, the constructed vascular trees are visualized by rendering the 3D trees and the 3D binary image together in a transparent display mode. The program is carried out in a fully automatic fashion, with a few default settings. Occasionally, user intervention is needed at the 3D segmentation stage to impose an appropriate threshold when the automatic 3D segmentation is obviously sub-optimal for vessel delineation. Experimental demonstrations on both coronary artery phantom and a cast of coronary artery tree of a swine animal model are provided.

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.

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 μm were reconstructed from cast data while vessels < 40 μm 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.

Neoplastic Transformation In Vitro after Exposure to Low Doses of Mammographic-Energy X Rays: Quantitative and Mechanistic Aspects

Abstract Ko, S. J., Liao, X-Y., Molloi, S., Elmore, E. and Redpath, J. L. Neoplastic Transformation In Vitro after Exposure to Low Doses of Mammographic-Energy X Rays: Quantitative and Mechanistic Aspects. Radiat. Res. 162, 646–654 (2004). The induction of neoplastic transformation in vitro after exposure of HeLa × 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.

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.

ACCURACY OF QUANTIFYING CORONARY HYDROXYAPATITE WITH ELECTRON BEAM TOMOGRAPHY

RATIONALE AND OBJECTIVES. The electron beam tomography coronary calcium score continues to be used without experimental validation. To determine its accuracy, a series of experiments was performed. METHODS.A chest phantom model was constructed with coronary arteries represented by cylindrical holes containing hydroxyapatite granules embedded in a gelatin matrix to simulate coronary arteries. Experiments were performed to determine the relationship between the mass of hydroxyapatite in each of these arteries, the coronary calcium score currently used in coronary screening, and an alternative method of estimating mass from the images. The model was scanned with equal amounts of hydroxyapatite in each artery: 1) when the cylindrical heart was rotated 36 degrees 10 times between scans, and 2) when the particle diameters varied from 0.1 mm to 4 mm. The scores were calculated, and a subtraction algorithm was applied to estimate the exact mass of hydroxyapatite in each artery. RESULTS. The hydroxyapatite scores varied by 42% with position and by 1.54 X 106% with particle diameter. The estimated masses from the subtraction algorithm were more stable with position and particle size, with maximum percent errors of 10% and 14% for position and particle size, respectively. CONCLUSIONS.These results suggest that the coronary calcium score is invalid, and that more precise and clinically relevant methods, such as the arterial summation method, should be rigorously tested in clinical studies.