Imaging of nanoparticles with dual-energy computed tomography

A simulation study was performed to determine the feasibility and performance of imaging nanoparticles as contrast agents in dual-energy computed tomography. An analytical simulation model was used to model the relevant signal-to-noise ratio (SNR) in dual-energy imaging for the specific case of a three-material patient phantom consisting of water, calcium hydroxyapatite and contrast agent. Elemental gold and iodine were both considered as contrast agents. Simulations were performed for a range of monoenergetic (20-150 keV) and polyenergetic (20-150 kVp) beam spectra. A reference configuration was defined with beam energies of 80 and 140 kVp to match current clinical practice. The effect of adding a silver filter to the high-energy beam was also studied. A figure of merit (FOM), which normalized the dual-energy SNR to the square root of the patient integral dose, was calculated for all cases. The units of the FOM were keV(-1/2). A simple Rose model of detectability was used to estimate the minimum concentration of either elements needed to be detected (SNR > 5). For monoenergetic beams, the peak FOM of gold was 6.4 × 10(-6) keV(-1/2), while the peak FOM of iodine was 3.1 × 10(-6) keV(-1/2), a factor of approximately 2 greater for gold. For polyenergetic spectra, at the reference energies of 80 and 140 kVp, the FOM for gold and iodine was 1.65 × 10(-6) and 5.0 × 10(-7) keV(-1/2), respectively, a factor of approximately 3.3 greater. Also at these energies, the minimum detectable concentration of gold was estimated to be 58.5 mg mL(-1), while iodine was estimated to be 117.5 mg mL(-1). The results suggest that the imaging of a gold nanoparticle contrast agent is well suited to current conditions used in clinical imaging. The addition of a silver filter of 800 μm further increased the image quality of the gold signal by approximately 50% for the same absorbed dose to the patient.     

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.     

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.     

Quantification of coronary arterial calcium by dual energy digital subtraction fluoroscopy

Clinical studies of the heart with fluoroscopy have shown that fluoroscopic visualization of calcium in the coronary arteries is strongly associated with coronary artery disease. However, fluoroscopic detection is limited by its low sensitivity, which is partly due to the interfering background tissue structures and image quantum noise. Moreover, quantification of the absolute amount of calcium in an arterial segment has not been possible. A real-time dual-energy subtraction technique has been investigated as a possible solution to the above problem. In this energy subtraction technique, the kVp and filtration are switched at 30 Hz. In order to assess the potential utility of this videodensitometric technique to quantitate coronary artery calcium, arterial phantoms and excised segments of diseased human arteries were imaged. The low- and high-energy images were corrected for scatter and veiling glare before subtraction. Calcium measurements were made using the tissue-suppressed energy-subtracted images. The estimated calcium phosphate and ashed weights of the calcified arterial segments (N = 20) were highly correlated (slope = 1.04, Intercept = -0.33 mg, r = 0.92).     

Positron autoradiography for intravascular imaging: feasibility evaluation

Approximately 70% of acute coronary artery disease is caused by unstable (vulnerable) plaques with an inflammation of the overlying cap and high lipid content. A rupturing of the inflamed cap of the plaque results in propagation of the thrombus into the lumen, blockage of the artery and acute ischaemic syndrome or sudden death. Morphological imaging such as angiography or intravascular ultrasound cannot determine inflammation status of the plaque. A radiotracer such as 18F-FDG is accumulated in vulnerable plaques due to higher metabolic activity of the inflamed cap and could be used to detect a vulnerable plaque. However, positron emission tomography (PET) cannot detect the FDG-labelled plaques because of respiratory and heart motions, small size and low activity of the plaques. Plaques can be detected using a miniature particle (positron) detector inserted into the artery. In this work, a new detector concept is investigated for intravascular imaging of the plaques. The detector consists of a storage phosphor tip bound to the end of an intravascular catheter. It can be inserted into an artery, absorb the 18F-FDG positrons from the plaques, withdrawn from the artery and read out. Length and diameter of the storage phosphor tip can be matched to the length and the diameter of the artery. Monte Carlo simulations and experimental evaluations of coronary plaque imaging with the proposed detector were performed. It was shown that the sensitivity of the storage phosphor detector to the positrons of 18F-FDG is sufficient to detect coronary plaques with 1 mm and 2 mm sizes and 590 Bq and 1180 Bq activities in the arteries with 2 mm and 3 mm diameters, respectively. An experimental study was performed using plastic tubes with 2 mm diameter filled with an FDG solution, which simulates blood. FDG spots simulating plaques were placed over the surface of the tube. A phosphor tip was inserted into the tube and imaged the plaques. Exposure time was 1 min in all simulations and experiments. Experiments showed that detecting the coronary plaques using the proposed technique is possible. The proposed technique has the potential for fast and accurate detection of vulnerable coronary and other intravascular plaques.     

Regional volumetric coronary blood flow measurement by digital angiography: in vivo validation

RATIONALE AND OBJECTIVES: There are well-known limitations to the use of visual estimation to assess the severity of coronary artery disease and luminal stenosis. This is especially true in the case of an intermediate coronary lesion (30%-70% diameter stenosis), where coronary arteriography is very limited in distinguishing ischemia-producing intermediate coronary lesions from non-ischemia-producing ones. For this reason, a functional measure of stenosis severity is desirable. The goal of this study is to validate a video densitometry technique for quantitative assessment of regional volumetric coronary blood flow. MATERIALS AND METHODS: Coronary arteriography was performed in eight swine (body weight, 25-50 kg) after power injection of contrast material into the left main coronary artery. Phase-matched subtracted images were used to quantify regional coronary blood flow using a video densitometry technique. The in vivo regional flow measurements were validated using a transit time ultrasound flow probe. RESULTS: In 44 measurements, the ultrasound (Q(US)) and video densitometry (Q(VD)) regional flow measurements were related by Q(VD) = 0.98 Q(US) + 0.11 mL/min (r = 0.98). The results of mean regional coronary blood flow measurements for repeated coronary arteriograms of the first (Q(VD1)) and second (Q(VD2)) measured flows were related by Q(VD1) = 1.04 Q(VD2) + 0.05 mL/min (r = 0.97). CONCLUSIONS: A video densitometry technique for quantification of regional coronary blood flow was validated using a swine animal model. The results demonstrated the feasibility and potential utility of the video densitometry technique for accurate measurement of regional coronary blood flow, in vivo. This study provides an angiographic method that can potentially be used to evaluate intermediate coronary lesions during routine coronary arteriography.     

In vivo validation of the design rules of the coronary arteries and their application in the assessment of diffuse disease

The conventional rationale that uses per cent diameter reduction to assess diffuse coronary artery disease is not appropriate because no normal reference segments exist. In a recent publication, we have proposed a theoretical model based on physical principles that relate the various morphological and haemodynamic parameters (cross-sectional area, length, volume and flow) of the normal coronary arterial tree. The model was validated using haemodynamic simulations based on detailed morphological data of the pig coronary arterial tree. This paper extends the model validation to in vivo swine studies. Coronary arteriography was performed in five swine (15-18 kg body weight) after power injection of contrast material into the coronary artery. Coronary arterial length was obtained using a 3D reconstruction technique. The arterial volume, cross-sectional area and blood flow were measured using videodensitometry. The proposed relationships between these quantities were validated. Furthermore, a sensitivity analysis was demonstrated based on a simulation of diffuse coronary artery disease (approximately 40% reduction in cross-sectional area). The results of a sensitivity analysis based on a simulation of diffuse coronary artery disease suggest that the relationships between arterial volume, cross-sectional area, blood flow and the distal arterial length can be utilized to quantify moderate levels of diffuse coronary artery disease.     

Assessment of vasoreactivity using videodensitometry coronary angiography

Background: Previous studies demonstrated that the dysfunction of vasomotor tone (VT) is closely linked to the development of atherosclerosis and it is considered important in the very early stages of atherogenesis. Currently, the evaluation of VT relies on lumen changes in response to vasoactive stimuli using quantitative coronary angiography (QCA) based on geometric edge detection (ED). However, using ED for measuring lumen diameters is inherently associated with large uncertainties. Videodensitometry (VD) methods have important advantages over ED for QCA. The objective of this study was to investigate the reliability of VD and ED techniques in determining the effect of nitroglycerin (NTG) on cross-sectional area (CSA) and volume changes in a swine animal model for evaluating coronary vasoreactivity. Methods and results: Coronary angiography was performed on four anesthetized swine. CSA and volume were measured in the left anterior descending (LAD) coronary artery using VD before and after intracoronary injection of 0.3 mg of NTG. CSA was also calculated using standard QCA based on ED. The average CSA changes in the proximal, middle and distal branches measured using VD were 23.83% (±10.76%), 30.78% (±18.39%), and 27.34% (±36.53%), respectively. Similarly, the average CSA changes in the proximal, middle, and distal branches measured using ED were 15.02% (±36.38%), 22.02% (±26.12), and 38.00% (±48.31%), respectively. The average lumen volume change measured using VD was 29.79% (±14.79%). In order to evaluate the relative reliability of the techniques, the significance of deviation (SOD) was calculated, which is the ratio of the change after NTG and the measurement error. The average SOD for CSA for all the branches based on VD and ED were 1.86 and 0.69, respectively. The SOD for volume measurement was 2.78. Conclusions: Lumen changes measured by VD showed substantial improvement in reliability when compared to the ED. Moreover, VD can be used to measure substantially smaller changes in lumen dimension in response to vasoactive stimuli than the standard QCA based on ED. Finally, VD allows the measurement of arterial volume, which is not possible with ED.