Specific refraction-index increments of oxygenated hemoglobin from thalassemia-minor patients are not significantly different than those from healthy individuals.

The mass and concentration of hemoglobin per erythrocyte are important hematological parameters. Measuring these parameters from intact erythrocytes requires the value of specific refraction-index increment (RII) of oxygenated hemoglobin, which diverges in the literature. Refractive indices of hemoglobin solutions are measured directly by digital holographic microscopy on a microfluidic channel filled with hemoglobin solutions prepared by hemolysis of fresh human erythrocytes and refractive-index standards sequentially. Hemoglobin extracted from thalassemic patients shows 3-4% higher RII than that from healthy volunteers, but the difference is not significant in comparison to inter-subject variations within each group. The quantified RIIs are applied to quantify mean corpuscular hemoglobin mass of blood from 37 human subjects, and results are in accord with standard clinical test results.

Automatic detection and characterization of quantitative phase images of thalassemic red blood cells using a mask region-based convolutional neural network.

SIGNIFICANCE: Label-free quantitative phase imaging is a promising technique for the automatic detection of abnormal red blood cells (RBCs) in real time. Although deep-learning techniques can accurately detect abnormal RBCs from quantitative phase images efficiently, their applications in diagnostic testing are limited by the lack of transparency. More interpretable results such as morphological and biochemical characteristics of individual RBCs are highly desirable. AIM: An end-to-end deep-learning model was developed to efficiently discriminate thalassemic RBCs (tRBCs) from healthy RBCs (hRBCs) in quantitative phase images and segment RBCs for single-cell characterization. APPROACH: Two-dimensional quantitative phase images of hRBCs and tRBCs were acquired using digital holographic microscopy. A mask region-based convolutional neural network (Mask R-CNN) model was trained to discriminate tRBCs and segment individual RBCs. Characterization of tRBCs was achieved utilizing SHapley Additive exPlanation analysis and canonical correlation analysis on automatically segmented RBC phase images. RESULTS: The implemented model achieved 97.8% accuracy in detecting tRBCs. Phase-shift statistics showed the highest influence on the correct classification of tRBCs. Associations between the phase-shift features and three-dimensional morphological features were revealed. CONCLUSIONS: The implemented Mask R-CNN model accurately identified tRBCs and segmented RBCs to provide single-RBC characterization, which has the potential to aid clinical decision-making.

Morphometric analysis of erythrocytes from patients with thalassemia using tomographic diffractive microscopy.

Complete blood count is the most common test to detect anemia, but it is unable to obtain the abnormal shape of erythrocytes, which highly correlates with the hematologic function. Tomographic diffractive microscopy (TDM) is an emerging technique capable of quantifying three-dimensional (3-D) refractive index (RI) distributions of erythrocytes without labeling. TDM was used to characterize optical and morphological properties of 172 erythrocytes from healthy volunteers and 419 erythrocytes from thalassemic patients. To efficiently extract and analyze the properties of erythrocytes, we developed an adaptive region-growing method for automatically delineating erythrocytes from 3-D RI maps. The thalassemic erythrocytes not only contained lower hemoglobin content but also showed doughnut shape and significantly lower volume, surface area, effective radius, and average thickness. A multi-indices prediction model achieved perfect accuracy of diagnosing thalassemia using four features, including the optical volume, surface-area-to-volume ratio, sphericity index, and surface area. The results demonstrate the ability of TDM to provide quantitative, hematologic measurements and to assess morphological features of erythrocytes to distinguish healthy and thalassemic erythrocytes.

Precancerous esophageal epithelia are associated with significantly increased scattering coefficients.

The progression of epithelial precancers into cancer is accompanied by changes of tissue and cellular structures in the epithelium. Correlations between the structural changes and scattering coefficients of esophageal epithelia were investigated using quantitative phase images and the scattering-phase theorem. An ex vivo study of 14 patients demonstrated that the average scattering coefficient of precancerous epithelia was 37.8% higher than that of normal epithelia from the same patient. The scattering coefficients were highly correlated with morphological features including the cell density and the nuclear-to-cytoplasmic ratio. A high interpatient variability in scattering coefficients was observed and suggests identifying precancerous lesions based on the relative change in scattering coefficients.

Left ventricle segmentation in dynamic cardiac CT using random walks method.

PURPOSE: Segmentation of the left ventricle (LV) in cardiac CT (CCT) images is difficult due to the intensity heterogeneity arising from accumulation of contrast agent in papillary muscle and trabeculae carneae. In this study, we demonstrated the random walks method for LV segmentation in CCT through cardiac phases. METHODS: 63 CCT data sets from 7 patients with 9 cardiac phases were included in this study. All cardiac CT examinations were performed with GE 64-detector CT scanner with ECG gating. In each patient, 60-80 ml iohexol was injected at a flow rate of 5 ml/sec followed by 60 ml normal saline solution. Random walks (RW) based on probability of labels was used for LV segmentation. The LV delineations generated by the experienced physician (MD), conventional image-based method (IB), and RW were compared. RESULTS: In general the contours segment the LV closely by RW and MD, but the discrepancies in papillary muscle and trabeculae carneae were observed while using the IB method. CONCLUSION: We showed the RW method potentially improved LV segmentation as compared to the volume by conventional IB method. In this study, we demonstrated the clinical feasibility of LV volume segmentation using random walks algorithm.

Quantitative analysis of respiration-related movement for abdominal artery in multiphase hepatic CT.

OBJECTIVES: Respiration-induced motion in the liver causes potential errors on the measurement of contrast medium in abdominal artery from multiphase hepatic CT scans. In this study, we investigated the use of hepatic CT images to quantitatively estimate the abdominal artery motion due to respiration by optical flow method. MATERIALS AND METHODS: A total of 132 consecutive patients were included in our patient cohort. We apply the optical flow method to compute the motion of the abdominal artery due to respiration. RESULTS: The minimum and maximum displacement of the abdominal artery motion were 0.02 and 30.87 mm by manual delineation, 0.03 and 40.75 mm calculated by optical flow method, respectively. Both high consistency and correlation between the present method and the physicians' manual delineations were acquired with the regression equation of movement, y = 0.81x + 0.25, r = 0.95, p < 0.001. CONCLUSION: We estimated the motion of abdominal artery due to respiration using the optical flow method in multiphase hepatic CT scans and the motion estimations were validated with the visualization of physicians. The quantitative analysis of respiration-related movement of abdominal artery could be used for motion correction in the measurement of contrast medium passing though abdominal artery in multiphase CT liver scans.

Ventricular hemodynamics using cardiac computed tomography and optical flow method.

Ventricular hemodynamics plays an important role in assessing cardiac function in clinical practice. The aim of this study was to determine the ventricular hemodynamics based on contrast movement in the left ventricle (LV) between the phases in a cardiac cycle recorded using an electrocardiography (ECG) with cardiac computed tomography (CT) and optical flow method. Cardiac CT data were acquired at 120 kV and 280 mA with a 350 ms gantry rotation, which covered one cardiac cycle, on the 640-slice CT scanner with ECG for a selected patient without heart disease. Ventricular hemodynamics (mm/phase) were calculated using the optical flow method based on contrast changes with ECG phases in anterior-posterior, lateral and superior-inferior directions. Local hemodynamic information of the LV with color coating was presented. The visualization of the functional information made the hemodynamic observation easy.

Quantitative analysis of digital subtraction angiography using optical flow method on occlusive cerebrovascular disease.

BACKGROUND AND PURPOSE: Traditional digital subtraction angiography (DSA) provides detailed spatial resolution in the treatment of cerebrovascular disease. However, the available temporal information is often underutilized. The purpose of this study is to use deformable image registration with DSA to quantify the hemodynamic improvement of intracranial vessels after carotid stenting. MATERIALS AND METHODS: Eighteen patients with carotid stenosis (greater than 70% degree by NASCET criteria) were treated using percutaneous transluminal angioplasty with stents. Carotid angiograms of the anterior-posterior and lateral views were acquired before and after the treatment. The arterial and venous phases of each single acquisition were classified according to the first arrival time of contrast in the distal middle cerebral artery and the superior sagittal sinus, respectively. The optical flow method was subsequently applied to determine the blood flow velocity in intracranial vessels. Blood flow velocity comparisons were performed to determine the therapeutic effects of blood flow restoration. RESULTS: The pixel-by-pixel blood flow velocity was estimated using the optical flow method. A color scale was used in the visualization and estimation of the blood flow velocity in the vascular bed. The improvements of blood flow velocity in both the arterial and the venous phases were significant (p<0.05). The changes with contrast agent motion were more easily observed in the arterial phase compared with the venous phases. CONCLUSION: Quantitative digital subtraction angiography provides reliable blood flow velocity measurements, which facilitates pretherapeutic evaluation and a reliable follow-up analysis method for the evaluation of occlusive vascular disorder treatment in the head and neck regions.

Improvement of internal tumor volumes of non-small cell lung cancer patients for radiation treatment planning using interpolated average CT in PET/CT.

Respiratory motion causes uncertainties in tumor edges on either computed tomography (CT) or positron emission tomography (PET) images and causes misalignment when registering PET and CT images. This phenomenon may cause radiation oncologists to delineate tumor volume inaccurately in radiotherapy treatment planning. The purpose of this study was to analyze radiology applications using interpolated average CT (IACT) as attenuation correction (AC) to diminish the occurrence of this scenario. Thirteen non-small cell lung cancer patients were recruited for the present comparison study. Each patient had full-inspiration, full-expiration CT images and free breathing PET images by an integrated PET/CT scan. IACT for AC in PET(IACT) was used to reduce the PET/CT misalignment. The standardized uptake value (SUV) correction with a low radiation dose was applied, and its tumor volume delineation was compared to those from HCT/PET(HCT). The misalignment between the PET(IACT) and IACT was reduced when compared to the difference between PET(HCT) and HCT. The range of tumor motion was from 4 to 17 mm in the patient cohort. For HCT and PET(HCT), correction was from 72% to 91%, while for IACT and PET(IACT), correction was from 73% to 93% (*p<0.0001). The maximum and minimum differences in SUVmax were 0.18% and 27.27% for PET(HCT) and PET(IACT), respectively. The largest percentage differences in the tumor volumes between HCT/PET and IACT/PET were observed in tumors located in the lowest lobe of the lung. Internal tumor volume defined by functional information using IACT/PET(IACT) fusion images for lung cancer would reduce the inaccuracy of tumor delineation in radiation therapy planning.

Quantitative flow measurement by digital subtraction angiography in cerebral carotid stenosis using optical flow method.

OBJECTIVE: We analyzed intracranial regional blood flows using an optical flow method (OFM) and digital subtraction angiography in patients with internal carotid artery (ICA) stenosis. We also retrospectively explored the correlation between the patients' diagnoses and the severity of the ICA stenoses. MATERIALS AND METHODS: OFM, an image-processing algorithm to estimate motion, was applied to determine the mean velocity V(mean) in the vessels. A group of 40 patients without vascular anomalies acted as the control group. The patients were classified as having either moderate stenosis (< 80%, n=14) or severe stenosis (> 80%, n=23). RESULTS: The V(mean) of the ICAs was significantly lower in the stenotic group compared with the control group (p< 0.01). The V(mean) of the ICAs was inversely correlated with the severity of the stenosis (p< 0.05). The receiver operating characteristic curve of the V(mean) in an AP view showed substantial discriminatory power, with an optimal cutoff value of 3.48 pixels/frame for the detection of patients with carotid stenosis. The sensitivity and specificity were 84% and 50%, respectively. On a lateral view, the best cutoff for the V(mean) was 4.01 pixels/frame, and the sensitivity and specificity were 92% and 43%, respectively. CONCLUSIONS: Digital subtraction angiography combined with the OFM is a feasible parametric method for intracranial blood flow measurements in patients with moderate to severe carotid stenosis.

Quantitative portal vein velocity of liver cancer patients with transcatheter arterial chemoembolization on angiography.

OBJECTIVE: We applied optical flow method (OFM) to quantify relative velocities of blood flow using digital subtraction angiography (DSA) in the vascular analysis of hepatocellular carcinoma (HCC) patients who underwent transarterial chemoembolization (TACE) treatment. METHODS: A total of 40 HCC patients treated by TACE were analyzed in this study. DSA imaging with a 12-inch field of view, 1024 × 1024 pixels and 4 frames/second was acquired. OFM developed for motion estimation is applied for blood flow estimation. Two acrylic phantoms were built to validate the method. RESULTS: The relationship between the OFM and Doppler measurements was found linear with R(2) = 0.99 for both straight and curved tube phantoms. Quantitative blood flow distribution images of the portal vein region were presented. After TACE, the minimum, maximum and mean velocities in the portal vein all decreased (P < 0.05). Additionally, the velocity in the portal vein is significantly lower with a higher Child-Pugh score (P < 0.01). CONCLUSIONS: The present technique provides add-on quantitative information of flows to DSA and the hemodynamic analysis in relative quantifications of blood flow in portal vein of hepatocellular carcinoma patients using DSA.

Hemodynamic analysis of vascular stenting treatment outcome: computational fluid dynamics method vs optical flow method.

BACKGROUND AND PURPOSE: Computational fluid dynamics method (CFDM) and optical flow method (OFM) effectively provide the hemodynamic information based on the digital subtraction angiogram (DSA). However, the quantitative analysis in comparison of CFDM and OFM is still absent. The goal of this study is to apply CFDM and OFM in quantitative analysis of stenting treatment. MATERIAL AND METHOD: A left carotid stenosis patient underwent stenting of percutaneous transluminal angioplasty was analyzed as an example. CFDM and OFM for hemodynamic analysis on digital subtraction angiography before and after stenting treatment were presented. RESULTS: Improvement gains of blood flow velocities on left internal carotid artery after stenting treatment for different initial conditions on the common carotid artery were 1.91 ∼ 2.13, 1.62 ∼ 2.09, and 0.69 by CFDM with Newtonian and non-Newtonian fluids and OFM, respectively. With the CFDM analysis, the flow mapping by OFM using time resolved DSA data on the fly to estimate hemodynamic significance of a cervical carotid stenosis was explained. CONCLUSION: Quantificative blood flow estimations by CFDM and OFM to evaluate the treatment outcomes to patient with carotid stenosis are practical. Both methods are able to provide quantitative information of blood flow for stenting treatment. It is advantagious to use both methods in treatment evaluation.

An approach to automatic blood vessel image registration of microcirculation for blood flow analysis on nude mice.

Image registration is often a required and a time-consuming step in blood flow analysis of large microscopic video sequences in vivo. In order to obtain stable images for blood flow analysis, frame-to-frame image matching as a preprocessing step is a solution to the problem of movement during image acquisition. In this paper, microscopic system analysis without fluorescent labelling is performed to provide precise and continuous quantitative data of blood flow rate in individual microvessels of nude mice. The performance properties of several matching metrics are evaluated through simulated image registrations. An automatic image registration programme based on Powell's optimisation search method with low calculation redundancy was implemented. The matching method by variance of ratio is computationally efficient and improves the registration robustness and accuracy in practical application of microcirculation registration. The presented registration method shows acceptable results in close requisition to analyse red blood cell velocities, confirming the scientific potential of the system in blood flow analysis.