Videodensitometric analysis of coronary stenoses. In vivo geometric and physiologic validation in humans

Assessment of the severity of coronary stenoses on arteriograms conventionally is based on subjective estimates of percent luminal diameter narrowing. However, in studies in patients with multivessel coronary artery disease, we have found a poor correlation between percent stenosis and the physiologic significance of an individual coronary obstruction. The purpose of this study was to determine whether computerized videodensitometry would allow estimation of coronary luminal area and therefore prediction of the physiologic significance of individual coronary stenoses in humans. Videodensitometry was used to define the minimal luminal area of 15 left anterior descending, 15 circumflex, and 15 right coronary artery segments in 43 patients. Computer-assisted quantitative coronary arteriography (method of Brown et al) was used to determine the minimal luminal cross-sectional area of these same segments. In each arterial segment, coronary vasodilator reserve was assessed using intraoperative (n = 18 segments) or intracoronary (n = 27 segments) Doppler measurements of coronary vasodilator reserve. Videodensitometric estimates of coronary luminal area correlated well with minimal luminal area defined using the independent geometric technique of quantitative coronary arteriography (r = 0.82, y = 0.97 X + 0.71, SEE = 1.83 mm2, n = 45) and with lesion physiologic significance as defined by studies of the peak-to-resting velocity ratio (r = 0.71, 0.92, and 0.74 for the left anterior descending, circumflex, and right coronary arteries, respectively). Thus, videodensitometry is a promising method that may supplement geometric approaches to quantitative analysis of coronary arteriograms in humans.     

Plow quantitation with echo-planar phase-contrast velocity mapping: In vitro and in vivo evaluation

We present a multishot echo-planar imaging (EPI) phase-contrast implementation for flow quantitation. The measurement accuracy of this technique was evaluated in vitro and in vivo. A gated eight-shot EPI phase-contrast sequence (TR/TE = 16/7.4, 45° flip angle), with a flow-phase interval of 32 msec and an in-plane resolution of 2× 2 mm was initially evaluated in a pulsatile flow phantom. Subsequently, EPI phase-contrast flow measurements of the ascending and descending aorta, obtained in 10 volunteers, were compared with flow volume data acquired with a conventional cine phase-contrast sequence (TR/TE = 24/7, 45° flip angle, 48-msec flow-phase interval, 2 × 1 mm in-plane resolution). Comparisons between flow measurements were made using data obtained with the flow probe and cine phase contrast as the standard of reference for in vitro and in vivo measurements, respectively. EPI phase-contrast sequences reduced data acquisition times tenfold compared with cine phase-contrast sequences. EPI phase-contrast flow measurements correlated were with phantom flow (r = 0.98, slope = 1.1) as well as with aortic cine phase-contrast flow volume determinations (r = 0.98). A 95% confidence interval of measurement differences between echo-planar and cine phase-contrast imaging, ranging from 2.0 to - 1058 mL/min was computed. Ultrafast phase-contrast flow measurements are possible. Multishot EPI phase-contrast imaging provides high measurement accuracy in pulsatile vessels while keeping the image acquisition interval short enough to be accomplished in a comfortable breath-hold.     

In vivo quantitation of regional cerebral blood flow in glioma and cerebral infarction: validation of the HIPDm-SPECT method

Iodine-123 labeled hydroxyiodopropyldiamine (HIPDm) is a diffusible indicator with an 85%-90% extraction fraction and stable retention in the brain for more than 2 hr. Equilibrium-phase imaging and quantitation using single-photon emission computed tomographic (SPECT) scanning defined a distribution of HIPDm in proportion to regional cerebral blood flow (rCBF). Studies in calves affirmed a close correspondence (r = 0.97) in calculated rCBF between HIPDm and microspheres using the tissue deposition-arterial input function microsphere methodology. Using this same mathematical analysis in vivo, reproducible rCBF data within the expected range of normal were obtained on repeated studies in the same nonhuman primate. With a diffuse encephalopathy secondary to subarachnoid blood, a bilaterally symmetric decrease in rCBF was present. A prominent focal decrease in HIPDm accumulation and calculated rCBF was noted with cerebral infarction in the distribution of a ligated middle cerebral artery. Patient studies with glioma revealed diminished HIPDm accumulation due to decreased flow and/or pH in the region of the neoplasm as well as in the associated vasogenic edema and overlying gray matter.     

Assessment of airways with three-dimensional quantitative thin-section CT: in vitro and in vivo validation

PURPOSE: To prospectively validate the ability of customized three-dimensional (3D) software to enable bronchial tree skeletonization, orthogonal reconstruction of the main bronchial axis, and measurement of cross-sectional wall area (WA) and lumen area (LA) of any visible bronchus on thin-section computed tomographic (CT) images. MATERIALS AND METHODS: Institutional review board approval and patient agreement and informed consent were obtained. Software was validated in a phantom that consisted of seven tubes and an excised human lung obtained and used according to institutional guidelines. In vivo validation was performed with multi-detector row CT in six healthy subjects (mean age, 47 years; range, 20-55 years). Intra- and interobserver agreement and reproducibility over time for bronchial tree skeletonization were evaluated with Bland-Altman analysis. Concordance in identifying bronchial generation was assessed with the kappa statistic. WA and LA obtained with the manual method were compared with WA and LA obtained with validated software by means of the Wilcoxon test and Bland-Altman analysis. RESULTS: WA and LA measurements in the phantom were reproducible over multiple sessions (P > .90) and were not significantly different from WA and LA assessed with the manual method (P > .62). WA and LA measurements in the excised lung and the subjects were not different from measurements obtained with the manual method (intraclass correlation coefficient > 0.99). All lobar bronchi and 80.8% of third generation bronchi, 72.5% of fourth generation bronchi, and 37.7% of fifth generation bronchi were identified in vivo. Intra- and interobserver agreement and reproducibility over time for airway skeletonization and concordance in identifying bronchial generation were good to excellent (intraclass correlation coefficient > 0.98, kappa > 0.54, respectively). CONCLUSION: This method enables accurate and reproducible measurement of WA and LA on reformatted CT sections perpendicular to the main axis of bronchi visible on thin-section CT scans.     

Computer-assisted quantitation of coronary artery stenosis

With the incorporation of the computer and sophisticated software in medical imaging, the digitized cine radiograph is revealing more information than ever before. This article explains the use of such tools in the quantitation of coronary arteries using the many geometric characteristics that are sometimes overlooked on the diseased vessel.     

Cine flow measurements using phase contrast with undersampled projections: in vitro validation and preliminary results in vivo

PURPOSE: To assess the accuracy of flow measurements in vitro and in vivo during scan times shorter than a breath-hold using a 2D cine phase contrast (PC) undersampled radial acquisition method, which may be useful for measuring flow, especially in vessels subject to motion during respiration. MATERIALS AND METHODS: For in vitro assessment, a flow phantom was imaged at various flow rates and undersampling factors. For in vivo assessment, five normal subjects were imaged and the flow rate in the aorta was compared with the sum of the flow rates in the iliac arteries. RESULTS: For results in vitro, the accuracy of flow measurements was maintained with scan times as low as 13-17 seconds. For results in vivo, scans acquired in less than 25 seconds provided flow measurements in the aorta that corresponded well to the sum of flow measurements in the iliac arteries. CONCLUSION: The undersampled radial acquisition cine PC technique provided accurate flow measurements in a flow phantom and in healthy human volunteers in scan times shorter than a typical breath-hold.     

Right and left lung perfusion: in vitro and in vivo validation with oblique-angle, velocity-encoded cine MR imaging

Quantification of pulmonary flow is clinically important in the evaluation of both congenital and acquired heart disease. Velocity-encoded cine magnetic resonance (MR) is a promising technique for measuring velocity and volume of blood flow. The authors report validation of the accuracy of velocity-encoded cine MR for measurement of oblique-angle flow in vitro, with use of a constant-flow phantom, and in vivo, with nine healthy volunteers in whom velocities were measured separately in the main, right, and left pulmonary arteries. Findings at MR were compared with findings at Doppler echocardiography. Velocity measurements in a flow phantom with cine MR correlated well with direct measurements at Doppler echocardiography. Velocity-encoded cine MR enabled accurate and reproducible measurement of absolute blood flow in healthy subjects. Oblique-gradient flow encoding (ie, flow-encoding direction coinciding with the true direction of flow) was the method of choice for velocity measurements in the right and left pulmonary arteries.     

Right and left ventricular stroke volume measurements with velocity-encoded cine MR imaging: in vitro and in vivo validation

The accuracy of measurements of flow velocity determined by using cine MR phase velocity mapping--velocity-encoded cine (VEC) MR--was assessed by comparing VEC MR data with independent measurements in a flow phantom and in human subjects. Constant flow velocities generated in a phantom (range, 20-408 cm/sec) were determined correctly by VEC MR (r = .997, standard error of the estimate [SEE] = 7.9 cm/sec). Peak systolic velocities in the main pulmonary artery determined by VEC MR correlated well with the measurements obtained by using continuous-wave Doppler echocardiography (r = .91). Stroke volumes measured at the aorta by VEC MR and continuous-wave Doppler imaging also correlated well with each other (r = .80). VEC MR measurements of aortic and pulmonary flow provided left and right ventricular stroke volumes that correlated well with left ventricular stroke volumes determined by short-axis cine MR images (r = .98, SEE = 3.7 ml, and r = .95, SEE = 4.8 ml, respectively). Intra- and interobserver variabilities were small for both left and right ventricular stroke volumes as measured with VEC MR. These results indicate that VEC MR accurately and reproducibly measures aortic and pulmonary flow velocities and volumes in the physiologic range of humans, and can be used to measure right and left ventricular stroke volumes under normal flow conditions.     

Faster flow quantification using sensitivity encoding for velocity-encoded cine magnetic resonance imaging: in vitro and in vivo validation

PURPOSE: To test the agreement between conventional and sensitivity-encoded (SENSE) velocity encoded cine (VEC) MRI in a flow phantom and in subjects with congenital and acquired heart disease. MATERIALS AND METHODS: Flow measurements were performed in a 1.5 T scanner using a segmented k-space VEC MRI sequence and then repeated with a SENSE factor of 2. The flow phantom used a piston pump to generate physiologic arterial waveforms (0.5-4.9 L/min). In the subjects, flow measurements were performed in the ascending aorta (N = 33) and/or the main pulmonary artery (N = 24). RESULTS: Utilization of SENSE reduced the scan time by 50%. In the phantom, measurements without and with SENSE agreed closely with a mean difference of 0.01 +/- 0.08 L/min or 0.12% +/- 3.8% (P = 0.68). In the subjects, measurements without and with SENSE also agreed closely with a mean difference of 0.08 +/- 0.36 L/min or 1.3% +/- 7.2% (P = 0.08). Compared with standard imaging, the use of SENSE reduced the signal-to-noise ratio (SNR) by 28% in the phantom (N = 10) and 27% in vivo (N = 22). CONCLUSION: VEC MRI flow measurements with a SENSE factor of 2 were twice as fast and agreed closely with the conventional technique in vitro and in vivo. VEC MRI with SENSE can be used for rapid and reliable quantification of blood flow.     

Assessment of pulmonary vasculature volume with automated threshold-based 3D quantitative CT volumetry: in vitro and in vivo validation

Objectives

To validate the ability of threshold-based 3D CT volumetry to enable measurement of volume of visible pulmonary vessels on CT.

Materials and methods

In vivo, 3D CT volumetry was validated in seven phantoms that consisted of silicone tubes embedded in a foam block. With the true volume value as reference standard, the accuracy of CT measurement at various lower thresholds of −600 HU, −500 HU, −300 HU and −200 HU were compared. The volume measurements obtained when filled with varied concentration of iodinated contrast media (1:100, 1:200 and 1:500) were also compared. In vivo validation was performed in sixteen patients (9 men, 7 women; mean age, 52.1 years). Inter-scan and inter-observer agreement and reproducibility for pulmonary vasculature volume measurement were evaluated with Bland–Altman analysis.

Results

In vitro, the mean value measured under lower threshold of −300 HU (relative error = 1.5%) were the closest to the true values and have no signi?cant difference (P = 0.375). There were no signi?cant differences among the phantom measurement values with different filled concentration (1:100, 1:200 and 1:500). In vivo, the inter-scan reproducibility of volume measurements was good, with a correlation coefficient of 0.82 and ICC (intraclass correlation coefficient) of 0.86. Inter-observer agreement was excellent with a correlation coefficient of 0.91 and ICC of 0.95.

Conclusions

The threshold-based 3D quantitative CT volumetry enables accurate and reproducible measurement of pulmonary vessels volume.     

Renal artery stenosis: in vivo perfusion MR imaging

The intravoxel incoherent motion (IVIM) model of perfusion and diffusion imaging was applied to an in vivo canine model of unilateral renal artery stenosis and was compared with relative renal blood flow determination with radioactive microspheres. The percentage relative renal blood flow as determined with radioactive microspheres correlated closely with the percentage apparent diffusion coefficient. If this method can be adapted to human imaging, it may provide a noninvasive means for detecting renal artery stenosis.     

In vivo SPECT quantitation of bone metabolism in hyperparathyroidism and thyrotoxicosis

Bone metabolism was assessed in vivo and noninvasively using quantitative SPECT. The effect of endocrine abnormalities on bone metabolism was studied in 27 patients with primary hyperparathyroidism (HPT) and 12 patients with thyrotoxicosis (TTX). Quantitative bone scintigraphy (QBS) values of 99mTc-MDP uptake were compared to normal values matched for sex and age. Bones with significantly increased QBS values indicating increased bone metabolism were identified in the two patient groups. Fifty-one percent of the bones in patients with HPT and 78% in patients with TTX showed significantly increased QBS values. Increase in bone metabolism was highest in the femoral shaft. Seven patients with HPT and five with TTX were successfully treated. Six patients with HPT and four patients with TTX showed significant decrease of bone metabolism with normal QBS values after three months. The results indicate that QBS can be used to evaluate bone metabolism and its response to treatment in individual bones in patients with endocrine abnormalities.     

Shear wave elastography of placenta: in vivo quantitation of placental elasticity in preeclampsia

PURPOSE

We aimed to evaluate the utility of shear wave elastography (SWE) for assessing the placenta in preeclampsia disease.

METHODS

A total of 50 pregnant women in the second or third trimester (23 preeclampsia patients and 27 healthy control subjects) were enrolled in the study. Obstetrical grayscale and Doppler ultrasonography, SWE findings of placenta, and prenatal/postnatal clinical data were analyzed and the best SWE cutoff value which represents the diagnosis of preeclampsia was determined. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of preeclampsia were calculated based on SWE measurements.

RESULTS

Mean stiffness values were much higher in preeclamptic placentas in all regions and layers than in normal controls. The most significant difference was observed in the central placental area facing the fetus where the umbilical cord inserts, with a median of 21 kPa (range, 3–71 kPa) for preeclampsia and 4 kPa (range, 1.5–14 kPa) for the control group (P < 0.01). The SWE data showed a moderate correlation with the uterine artery resistivity and pulsatility indices. The cutoff value maximizing the accuracy of diagnosis was 7.35 kPa (area under curve, 0.895; 95% confidence interval, 0.791–0.998); sensitivity, specificity, PPV, NPV, and accuracy were 90%, 86%, 82%, 92%, and 88%, respectively.

CONCLUSION

Stiffness of the placenta is significantly higher in patients with preeclampsia. SWE appears to be an assistive diagnostic technique for placenta evaluation in preeclampsia.Preeclampsia is one of the leading causes of maternal and perinatal morbidity and mortality, with preterm delivery occurring in approximately 5%–8% and perinatal mortality occurring in 1%–3% of pregnancies, worldwide (1). Common maternal complications of severe preeclampsia can include disseminated coagulopathy/HELLP syndrome, pulmonary edema, acute renal failure, placenta abruption, and long-term cardiovascular complications (2, 3). Common fetal complications are fetal growth restriction, preterm delivery, and perinatal death (4).The elasticity term defines the continuum mechanics of bodies that deform reversibly under strain. Shear wave elastography (SWE) is a novel ultrasonography (US) technique which is used to obtain elasticity information that represents the constituent of soft tissues. The principle of the modality is based on inducing mechanical vibration using acoustic radiation force, gathering the transverse shear waves that propagate laterally away from the tissue, and calculating their velocity. This kinetic method provides real-time quantitative data and has high reproducibility without compression effects/artifacts, as well as a deeper tissue response compared to static elastography (5, 6). We hypothesized that using noninvasive SWE to identify global structural disorganization of the placenta due to preeclampsia pathogenesis would help to detect the disease. To the best of our knowledge, the application of SWE for placental evaluation in preeclampsia has not been studied previously. In the present study, we inspected the SWE values related to changes in placental elasticity in preeclampsia and determined its utility for assessing the disease.     

Quantification of multicontrast vascular MR images with NLSnake,an active contour model: In vitro validation and in vivo evaluation

Vessel‐wall measurements from multicontrast MRI provide information on plaque structure and evolution. This requires the extraction of numerous contours. In this work a contour‐extraction method is proposed that uses an active contour model (NLSnake) adapted for a wide range of MR vascular images. This new method employs length normalization for the purpose of deformation computation and offers the advantages of simplified parameter tuning, fast convergence, and minimal user interaction. The model can be initialized far from the boundaries of the region to be segmented, even by only one pixel. The accuracy and reproducibility of NLSnake endoluminal contours were assessed on vascular phantom MR angiography (MRA) and high‐resolution in vitro MR images of rabbit aorta. An in vivo evaluation was performed on rabbit and clinical data for both internal and external vessel‐wall contours. In phantoms with 95% stenoses, NLSnake measured 94.3% ± 3.8%, and the accuracy was even better for milder stenoses. In the images of rabbit aorta, variability between NLSnake and experts was less than interobserver variability, while the maximum intravariability of NLSnake was equal to 1.25%. In conclusion, the NLSnake technique successfully quantified the vessel lumen in multicontrast MR images using constant parameters. Magn Reson Med 51:370–379, 2004. © 2004 Wiley‐Liss, Inc.     

Toward individualized SAR models and in vivo validation

The specific absorption rate (SAR) is a limiting constraint in sequence design for high‐field MRI. SAR estimation is typically performed by numerical simulations using generic human body models. This entails an intrinsic uncertainty in present SAR prediction. This study first investigates the required detail of human body models in terms of spatial resolution and the number of soft tissue classes required, based on finite‐differences time‐domain simulations of a 3 T body coil. The numerical results indicate that a resolution of 5 mm is sufficient for local SAR estimation. Moreover, a differentiation between fatty tissues, water‐rich tissues, and the lungs was found to be essential to represent eddy current paths inside the human body. This study then proposes a novel approach for generating individualized body models from whole‐body water‐fat‐separated MR data and applies it to volunteers. The SAR hotspots consistently occurred in the arms due to proximity to the body coil as well as in narrow regions of the muscles. An initial in vivo validation of the simulated fields in comparison with measured B₁‐field maps showed good qualitative and quantitative agreement. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Simultaneous in vitro and in vivo validation of nitrogen-13-ammonia for the assessment of regional myocardial blood flow

Measurement of myocardial blood flow by 13NH3 relies heavily on the assessment of both the input function and the variable tissue extraction fraction. In six open-chest dogs, myocardial and arterial 13NH3 activity was measured both by in vitro sampling and by in vivo positron emission tomography (PET). Regional myocardial blood flow was forced to vary in the range 0.2-5 ml/min/g and actual values were assessed by in vitro counting of 153Gd microspheres. The ammonia input function was processed by: (a) total curve integration; (b) curve integration for 2 min; (c) integral of a fitted curve (gamma variate in vivo and exponential of the downslope in vitro). Method C brought to regional flow values which best approximated microspheres data. The in vitro correlation allows for correcting in vivo values for the flow-dependent extraction fraction. The method can be easily applied for regional myocardial blood flow measurements with PET in human studies.     

Radiosynthesis, in vitro validation, and in vivo evaluation of 18F-labeled COX-1 and COX-2 inhibitors.

In this article, we describe the radiosynthesis and evaluation of 18F-labeled cyclooxygenase (COX) inhibitors. 18F-SC63217 is selective to COX-1 and has a COX-1 inhibitory concentration of 50% (IC(50)) < 10 nmol/L and a COX-2 IC(50) > 100 micromol/L. 18F-SC58125 has IC(50) values of >100 micromol/L (COX-1) and <86 nmol/L (COX-2). METHODS: SC63217 and SC58125 were both labeled with 18F by nucleophilic displacement of a trimethylammonium triflate salt using a dedicated microwave cavity. Each compound was evaluated in vitro using a murine macrophage cell line (J774). COX-2 was stimulated in these cells by treatment with lipopolysaccharide and interferon-gamma. Both radiotracers were further investigated in vivo using rat biodistribution techniques. Brain uptake of the COX-2 inhibitor, 18F-SC58125, was further investigated by brain PET of a baboon. RESULTS: The in vitro studies showed that uptake of 18F-SC58125 was increased in stimulated cells and was totally inhibited by the addition of nonradioactive SC58125. In contrast, no increase in uptake was seen for 18F-SC63217. In the biodistribution experiments, 18F-SC63217 showed much higher uptake in the small intestine (an organ known to express high levels of COX-1) than did 18F-SC58125. Higher levels of 18F-SC58125 were observed in the kidney, an organ known to contain high levels of COX-2 rather than COX-1. 18F-SC58125 was retained in brain tissue. PET images of the baboon showed no regional distribution of the radiotracer in the brain. CONCLUSION: We have developed a radiosynthetic route that can yield 18F-labeled selective inhibitors of COX-1 or COX-2. Both compounds have been fully characterized in vitro and in vivo. Our results indicate that 18F-SC58125 has potential as a marker of COX-2 activity but that, because of high nonspecific binding, 18F-SC63217 was not a good choice as a marker of COX-1.