Cubosomes enhance drug permeability across the blood-brain barrier in zebrafish.

The potential of cubosomes to improve delivery of incorporated cargo to the brain was explored in zebrafish. Cubosomes were formulated with one of three stabilisers, Pluronic F68, Pluronic F127 or Tween 80, with the hypothesis that coating with Tween 80 will enable brain targeting of cubosomes as has been previously shown for polymeric nanoparticles. The physiochemical properties and the ability of the cubosomes to facilitate delivery of the model drug lissamine rhodamine (RhoB) into the brain was investigated. Distribution of cubosomes in the midbrain was also investigated by ultrastructural analysis via incorporation of octanethiol-functionalized gold nanoparticles. Cubosomes were typically 165-195 nm in size with a Pn3m (Pluronics) or Im3m (Tween 80) cubic phase internal structure. Cubosomes were injected intravenously into zebrafish larvae (12-14 days post fertilization) and the concentration of RhoB in the midbrain was determined by quantifying its fluorescence intensity. Uptake of RhoB was significantly greater in larvae injected with Tween 80 stabilized cubosomes as compared to a control suspension of RhoB or cubosomes stabilized with Pluronics. Collectively, we show for the first time that cubosomes can be functionalized to deliver drug across the BBB, offering new opportunities to overcome drug delivery issues across this formidable biological barrier.

Medical physics aspects of cancer care in the Asia Pacific region: 2014 survey results.

It was the aim of this work to assess and track the workload, working conditions and professional recognition of radiation oncology medical physicists (ROMPs) in the Asia Pacific region over time. In this third survey since 2008, a structured questionnaire was mailed in 2014 to 22 senior medical physicists representing 23 countries. As in previous surveys the questionnaire covered seven themes: 1 education, training and professional certification, 2 staffing, 3 typical tasks, 4 professional organisations, 5 resources, 6 research and teaching, and 7 job satisfaction. The response rate of 100% is a result of performing a survey through a network, which allows easy follow-up. The replies cover 4841 ROMPs in 23 countries. Compared to 2008, the number of medical physicists in many countries has doubled. However, the number of experienced ROMPs compared to the overall workforce is still small, especially in low and middle income countries. The increase in staff is matched by a similar increase in the number of treatment units over the years. Furthermore, the number of countries using complex techniques (IMRT, IGRT) or installing high end equipment (tomotherapy, robotic linear accelerators) is increasing. Overall, ROMPs still feel generally overworked and the professional recognition, while varying widely, appears to be improving only slightly. Radiation oncology medical physics practice has not changed significantly over the last 6 years in the Asia Pacific Region even if the number of physicists and the number and complexity of treatment techniques and technologies have increased dramatically.

Brief histories of medical physics in Asia-Oceania.

The history of medical physics in Asia-Oceania goes back to the late nineteenth century when X-ray imaging was introduced, although medical physicists were not appointed until much later. Medical physics developed very quickly in some countries, but in others the socio-economic situation as such prevented it being established for many years. In others, the political situation and war has impeded its development. In many countries their medical physics history has not been well recorded and there is a danger that it will be lost to future generations. In this paper, brief histories of the development of medical physics in most countries in Asia-Oceania are presented by a large number of authors to serve as a record. The histories are necessarily brief; otherwise the paper would quickly turn into a book of hundreds of pages. The emphasis in each history as recorded here varies as the focus and culture of the countries as well as the length of their histories varies considerably.

Computerised analysis of liver texture with correlation to needle biopsy.

AIM: To assist in tissue characterisation for the non-invasive diagnosis of diffuse fatty liver infiltration by providing quantitative indices of ultrasonic (US) backscatter with correlation to histology. METHODS AND MATERIALS: US images from patients referred to US-guided liver needle biopsy (LNB) for persistently elevated liver enzymes or serologically positive markers for viral hepatitis were recorded. The histopathological reports were reviewed. Steatosis, inflammation and degree of fibrosis were scored from 0 (normal) to 3 (severe). Patients with level 3 steatosis without inflammation or fibrosis were selected. US images from twenty-four healthy subjects served as control. Four textural indices were calculated for a selected ROI corresponding to the biopsy site. Sensitivity and specificity of discrimination between the two groups were evaluated. RESULTS: Fatty and healthy livers formed two distinct clusters. However, in all parametric subspaces there was a slight overlap between the groups with a few numbers of cases located across the dichotomy line.The sensitivity for all the indices was high (90 - 100 %). The specificity for each of the indices was moderate. The co-occurrence local homogeneity index yielded the highest specificity (88.5 %), with a sensitivity equivalent to two of the other indices (90 %). CONCLUSIONS: Highly accurate "ultrasonic biopsy" may be obtained for severe fatty liver. The described indices can serve as a tool in US computer- aided diagnosis (CAD) of diffuse parenchymal liver disease, in particular for severe steatosis of the liver.

MR angiography using spin-lock flow tagging.

A method for MR angiography using an RF labeling technique is suggested. The method utilizes a slice-selective spin-lock pulse sequence for tagging the spins of inflowing blood. The pulse sequence begins with a spatially selective 90 degrees (x) RF pulse, followed by a nonselective composite locking pulse of 135 degrees (y) - n[360 degrees (y)]-135 degrees (y) and by a 90 degrees (-x) pulse. A spoiler gradient is then applied. A rapid imaging stage, which yields a T(1)rho-weighted signal from the tagged spins, completes the sequence. Untagged spins are thoroughly dephased and consequently suppressed in the image. Thus, contrast is obtained without an injection of a contrast material or image subtraction. Furthermore, the flow of the tagged bolus can be visualized. The sequence was implemented on phantoms and on human volunteers using a 1.5T scanner. The results indicate the feasibility of the suggested sequence.

3-D surface reconstruction of multiple sclerosis lesions using spherical harmonics.

A new approach to approximate the 3-D shape of multiple sclerosis (MS) lesions and to calculate their volumes is presented. The suggested method utilizes sets of MS lesion contours taken from segmented MR images and approximates their 3-D surfaces by spherical harmonics. This method was applied to obtain 3-D reconstructions of in vivo and simulated MS lesions and to calculate their volumes. The results show good geometrical approximations of the original MS lesions' 3-D shapes and good consistency in volume estimation independent of the size of the lesions. The average volume estimation error was smaller than the commonly used technique of slice stacking (15.5 +/- 13.4% and 13.1 +/- 10.1% vs. 25.0 +/- 17.0%). The method presented here offers a tool for analyzing the geometrical characteristics of MS lesions in 3-D as well as their volumes. The geometrical information may potentially serve as an additional clinical index for monitoring the disease.

Three-dimensional automatic quantitative analysis of intravascular ultrasound images.

Intravascular ultrasound (IVUS) has established itself as a useful tool for coronary assessment. The vast amount of data obtained by a single IVUS study renders manual analysis impractical for clinical use. A computerized method is needed to accelerate the process and eliminate user-dependency. In this study, a new algorithm is used to identify the lumen border and the media-adventitia border (the external elastic membrane). Setting an initial surface on the IVUS catheter perimeter and using active contour principles, the surface inflates until virtual force equilibrium defined by the surface geometry and image features is reached. The method extracts these features in three dimensions (3-D). Eight IVUS procedures were performed using an automatic pullback device. Using the ECG signal for synchronization, sets of images covering the entire studied region and corresponding to the same cardiac phase were sampled. Lumen and media-adventitia border contours were traced manually and compared to the automatic results obtained by the suggested method. Linear regression results for vessel area enclosed by the lumen and media-adventitia border indicate high correlation between manual vs. automatic tracings (y = 1.07 x -0.38; r = 0.98; SD = 0.112 mm(2); n = 88). These results indicate that the suggested algorithm may potentially provide a clinical tool for accurate lumen and plaque assessment.

Volumetric imaging with ultrasonic spiral CT.

To examine the feasibility of implementing spiral computed tomography (CT) in ultrasonic imaging as a potential method for breast screening, an algorithm for x-ray spiral CT was applied to ultrasonic waves on a specially built ultrasonic tomographic system. Three-dimensional reconstructions of various phantoms were obtained. Spiral ultrasonic CT is feasible, and it may have clinical merit as a breast imaging method.

On the human left ventricular shape.

The geometry of the heart plays a major role in cardiac function. The purpose of this study was to characterize analytically the geometric properties of the left ventricular (LV) three-dimensional (3D) shape, while excluding the effects of aspect ratio and size. Two groups of human hearts were studied by Cine-CT. The first group was composed of 10 healthy volunteers and the second of 9 pathological hearts. The hearts were scanned from apex to base. The endocardial borders of each LV scan were traced and used to reconstruct the 3D LV at end-diastole (ED) and end-systole (ES). Using a special normalized helical shape descriptor, denoted "geometrical cardiogram" (GCG), the typical 3D normal ED and ES shapes were determined. These typical shapes were then analytically approximated via a discrete cosine transform (DCT). The shape of each LV was then investigated for its correspondence to five analytically defined shapes: (i) a cone, (ii) a sphere, including all ellipsoidal shapes, (iii) a cylinder, (iv) a truncated ellipsoid, and (v) the DCT approximation of the normal LV shape. The results indicate that the normal LV shape can be well approximated by using only seven coefficients of the DCT. Conicity was the only geometrical feature which did not change from ED to ES in the normal group of hearts. The most prominent shape difference between normal and abnormal hearts was the significantly reduced conicity of the latter. Conicity is an important feature of LV geometry. The possible contribution of the conical shape to LV ejection efficiency is also discussed.

Effect of aneurysmectomy on left ventricular shape and function: case studies.

The three dimensional (3D) conformational changes in three patients with large anterior aneurysm in the left ventricle (LV) were examined before and two years after aneurysmectomy by using 3D Cine-computerized tomography (CT). Endocardial and epicardial tracings of 6-9 short axis images encompassing the entire LV were used to reconstruct the LV in 3D. Thickness and percent thickening were calculated using our 3D-volume element approach. A regional wall stress index (stress/pressure) was calculated from regional curvature and thickness. The analysis showed that following resection of the aneurysm the end-diastolic volume was reduced from 257+/-39 to 183+/-39 ml, end-systolic volume from 172+/-39 to 92+/-46 ml and, ejection fraction increased from 34+/-7 to 51+/-13%. The endocardial aneurysm area decreased from 19.7+/-15.9 to 10.1+/-6.5 cm2, whereas the normal zone area was minimally reduced from 87.4+/-17.6 to 79.8+/-10.8 cm2. The percent thickening of the normal zone increased significantly. It is documented here for the first time by detailed 3D analysis that the resection of the LV aneurysm reduces the aneurysmal area and LV size and improves the global and regional function of the remote normal zone. Therefore, the 3D approach can help to design better surgical technique for this complex operation.

Automated detection and characterization of multiple sclerosis lesions in brain MR images.

In the present study an automatic algorithm for detection and contouring of multiple sclerosis (MS) lesions in brain magnetic resonance (MR) images is introduced. This algorithm automatically detects MS lesions in axial proton density, T2-weighted, gadolinium enhanced, and fast fluid attenuated inversion recovery (FLAIR) brain MR images. Automated detection consists of three main stages: (1) detection and contouring of all hyperintense signal regions within the image; (2) partial elimination of false positive segments (defined herein as artifacts) by size, shape index, and anatomical location; (3) the use of an artificial neural paradigm (Back-Propagation) for final removal of artifacts by differentiating them from true MS lesions. The algorithm was applied to 45 images acquired from 14 MS patients. The algorithm's sensitivity was 0.87 and the specificity 0.96. In 34 images, 100% of the lesions were detected. The algorithm potentially may serve as a useful preprocessing tool for quantitative MS monitoring via magnetic resonance imaging.

Noninvasive measurement of shortening in the fiber and cross-fiber directions in the normal human left ventricle and in idiopathic dilated cardiomyopathy.

BACKGROUND: Studies in anesthetized dogs have shown that myocardial fibers shorten approximately 8%. However, in the endocardium, shortening occurs to a much greater extent at 90 degrees to the fiber orientation ("cross-fiber shortening") than it does along the fiber direction. The purpose of this study was to estimate the extent of fiber and cross-fiber shortening in the normal human left ventricle and in patients with idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Ten normal subjects and nine patients with IDC were imaged with magnetic resonance tissue tagging. Finite strain analysis was used to calculate endocardial and epicardial shortening in the fiber and cross-fiber directions using anatomic fiber angles from representative autopsy specimens as references. Anatomic fiber angles were not different between normal subjects and IDC patients. Epicardial fiber strain was -0.14+/-0.01 in normal subjects and -0.08+/-0.01 in IDC patients (P<.0001 versus normal subjects). Epicardial cross-fiber strain was -0.08+/-0.01 in normal subjects and -0.06+/-0.01 in IDC patients (P=NS). Endocardial fiber strain was -0.16+/-0.01 in normal subjects and -0.09+/-0.01 in IDC patients (P<.0001), and endocardial cross-fiber strain was -0.26+/-0.01 in normal subjects and -0.15+/-0.01 in IDC patients (P<.0001). Cross-fiber shortening was greater than fiber shortening at the endocardium in both normal subjects (P<.0001) and IDC patients (P<.05). CONCLUSIONS: In normal humans, the direction of maximal deformation aligns with the fiber direction in the epicardium but is perpendicular to the fiber direction in the endocardium. When strain in a coordinate system aligned to the fibers is estimated, cross-fiber shortening is found to be the dominant shortening strain at the endocardium. Normal fiber shortening is 15%, and this is markedly reduced in IDC. The normal transition in fiber orientation through the wall is not altered in IDC, and cross-fiber shortening is still the dominant strain at the endocardium, suggesting that interactions between myocardial layers persist in these patients.

Pattern analysis of temporal changes in the carotid artery diameter under normal and pathological conditions.

Age-related and temporal cyclic changes in the left and right common carotid arteries (CCA) diameters were studied in two groups of subjects: (i) 11 healthy normotensive subjects (ages 19-72 years), and (ii) eight hypertensive subjects (ages 59-85 years), with various degrees of stenosis in their ICA. Cross-sectional images of the left and right CCA were acquired via an ultrasonic system. Images were digitized, and the contour of the arterial wall for each frame was manually traced. Assuming a circular geometry, the arterial diameter was calculated. Averaging four to six consecutive heart beats yielded the typical patterns of temporal diameter changes for both the left and right CCA. For the group of normal subjects, a typical pattern of the temporal diameter changes with a consistent left vs right peak diameter delay (LRPDD), with the right CCA preceding the left, was observed. Plotting the normalized left vs right CCA diameters yielded a typical loop (DDloop) which changed in the counter-clockwise direction from systole to diastole. For the group of hypertensive subjects, the LRPDD decreased or became negative with the left CCA preceding the right if the stenosis degree exceeded 50% (p < 0.01). The DDloop changed from a counterclockwise to a clockwise direction. For the group of normal subjects, end diastolic, end systolic diameters and the elastic index of the CCA increased with age while the relative systolic change in diameter decreased with age. For the group of hypertensive subjects, the relative systolic change in diameter was smaller, compared to normals (7.8 +/- 1.2% vs 10.7 +/- 3.1%, respectively; p < 0.05). The elastic index for this group was significantly higher compared to the normal subjects (1.4 +/- 0.3 vs 0.6 +/- 0.2 x 10(5) dynes/cm2, respectively; p < 0.001). These findings imply that patterns of CCA temporal diameter changes can indicate the existence of a pathological state.

Mathematical formulation for computing the performance of self expanding helical stents.

Stents are cylindrical devices implanted inside pathologic tubular passages within the body. The stents, which are made of metal or plastic, keep the passage open for flow (of blood, urine, air etc.) by applying radial pressure on the passage walls. In most cases the stents are selected empirically for each application. We introduce here a mathematical formula for computing the radial pressure induced by self expanding helical stents. The formula was verified experimentally for an urological stent using a special device. The results correlate well with the theoretical predictions (R = 0.997; y = 1.017 x -0.06 kg; SEE = 0.034, for forces and R = 0.9988; y = 1.04 x +8.7 mmHg; SEE = 25.3 for pressures). This formula can potentially serve as an analytical tool for selecting the most suitable stent for a given application.

Hybrid ultrasonic computed tomography.

Ultrasonic computed tomography can provide valuable information on tissue properties. However, the large number of projections required to obtain a high-resolution image renders it impractical for routine clinical use. B-scan imaging, on the other hand is very rapid, but mainly provides information on tissue morphology. An algorithm which fuses information from a compound B-scan image and a limited view speed of sound (SOS) tomographic reconstruction of an object is presented here. The algorithm is iterative and is based on the two-dimensional Taylor series expansion. The algorithm diminishes artifacts caused by tomographic reconstruction from too few projections and produces an image which depicts both tissue morphology and acoustic properties (SOS). Consequently, quantitative images can be acquired in a much shorter time than required by conventional tomography. This method may potentially find application in ultrasonic breast screening.

In vivo assessment of regional myocardial work in normal canine hearts using 3D tagged MRI.

A non-invasive method for assessing regional myocardial work is presented. The method utilizes tagged magnetic resonance images (MRI) obtained from two sets of orthogonal planes to mark and reconstruct 24 small myocardial cuboids at end-diastole (ED) and end-systole (ES) in the in vivo left ventricle (LV). Regional myocardial work is assessed by calculating the area enclosed by the endocardial wall tension-area (T-A) loop of each studied cuboid. The method was applied to six normal canine hearts. In addition, a global myocardial work index was obtained from the corresponding estimated pressure-volume (P-V) loops. The average work index calculated using the T-A loop was 0.242 +/- 0.088 J/100gr/beat, in agreement with the average index obtained from the P-V loop: 0.296 +/- 0.089 J/100gr/beat. The two indices correlate linearly with a correlation coefficient of 0.82.

Localization of ischemia in canine hearts using tagged rotated long axis MR images, endocardial surface stretch and wall thickening.

Tagged magnetic resonance imaging allows the noninvasive measurement of regional systolic myocardial deformations and helps localize ischemic regions in the left ventricle (LV). The objective of this study was to evaluate the potential accuracy of localizing ischemic regions in the LV using endocardial and epicardial data obtained from tagged rotated long axis images. Nine canine hearts with acute ischemia induced by coronary artery ligation were imaged along four long axis planes rotated around the LV long axis, at end diastole and end systole. Each plane was tagged by four parallel lines perpendicular to the LV long axis. Tracing the endocardial and epicardial intersection points of the tag lines, 24 myocardial cuboids were reconstructed for each LV at end diastole and end systole. Endocardial surface stretch and transmural systolic thickening were calculated for each cuboid. The functional data were compared to perfusion data obtained from postmortem monastral blue staining of the heart. The ability of each functional index to discriminate between ischemic and non-ischemic regions was assessed using the "t"-statistic. The potential accuracy in localizing ischemia was evaluated by studying the corresponding sensitivity-specificity curves. The results demonstrate that adequate discrimination and localization can be obtained with both functional indices. However, endocardial surface stretch is advantageous as it uses only endocardial data and can save 50% of the post-processing time.

Regional three-dimensional geometry of the normal human left ventricle using cine computed tomography.

The aim of this study is to provide accurate three-dimensional measurements of left ventricular geometrical indices in relation to regional myocardial function. The analysis of the three-dimensional regional geometry and function of left ventricles of ten normal human volunteers is based on three-dimensional reconstructions of the left ventricle from cine computed tomography images, at end diastole and end systole, demonstrating normal left ventricular spatial, geometrical, and functional variability. Regional wall thickness, curvature and surface normals, as well as wall thickening and endocardial wall motion, are calculated and mapped for the entire left ventricle. The circumferential asymmetry of the left ventricle is reflected by the smaller circumferential and meridional curvatures at the septum. Thickening is highest at the anterior and lateral walls. Longitudinally, circumferential curvature increases toward the apex, whereas both wall thickness and wall thickening at end systole are largest at the midventricular level, decreasing toward the apex and base. This study describes the circumferential and apex-to-base variations in regional left ventricular geometric parameters of the normal human left ventricle, using three-dimensional imaging and analysis.

Effects of afterload on regional left ventricular torsion.

OBJECTIVE: To determine if left ventricular torsion, as measured by magnetic resonance tissue tagging, is afterload dependent in a canine isolated heart model in which neurohumoral responses are absent, and preload is constant. METHODS: In ten isolated, blood perfused, ejecting, canine hearts, three afterloads were studied, while keeping preload constant: low afterload, high afterload (stroke volume reduced by approx. 50% of low afterload), and isovolumic loading (infinite afterload). RESULTS: There were significant effects of afterload on both torsion (P < 0.05) and circumferential shortening (P < 0.0005). Between low and high afterloads, at the anterior region of the endocardium only, where torsion was maximal, there was a significant reduction in torsion (15.1 +/- 2.2 degrees to 7.8 +/- 1.8 degrees, P < 0.05). Between high afterload and isovolumic loading there was no significant change in torsion (7.8 +/- 1.8 degrees to 6.2 +/- 1.5 degrees, P = NS). Circumferential shortening at the anterior endocardium was significantly reduced both between low and high afterload (-0.19 +/- 0.02 to -0.11 +/- 0.02, P < 0.0005), and also between high afterload and isovolumic loading (-0.11 +/- 0.02 to 0.00 +/- 0.02, P < 0.05). Plots of strains with respect to end-systolic volume demonstrated a reduction in both torsion and shortening with afterload-induced increases in end-systolic volume. Torsion, but not circumferential shortening, persisted at isovolumic loading. CONCLUSIONS: Maximal regional torsion of the left ventricle is afterload dependent. The afterload response of torsion appears related to the effects of afterload on end-systolic volume.