A Multicenter Case-control Study of the Effect of Acute Rejection and Cytomegalovirus Infection on Pneumocystis Pneumonia in Solid Organ Transplant Recipients.

BACKGROUND: Pneumocystis pneumonia (PCP) is associated with morbidity and mortality in solid organ transplant (SOT) recipients. In this case-control study, we determined the association between posttransplant PCP and 3 variables: cytomegalovirus (CMV) infection, allograft rejection, and prophylaxis. METHODS: Eight transplant centers participated. For each case (SOT recipient with PCP), 3-5 controls (SOT recipients without PCP) were included. Controls were matched to the cases based on transplant center, type of allograft, and date of transplantation (±6 months). RESULTS: We enrolled 53 cases and 209 controls. Transplant types included kidney (n = 198), heart (n = 30), liver (n = 15), kidney-pancreas (n = 14), and lung (n = 5). PCP occurred beyond 12 months after transplantation in 43 (81.1%) cases. Thirty-four cases (64.1%) required admission to the intensive care unit, and 28 (52.8%) had mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases, and 14 (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion of female sex (P = .009), kidney dysfunction (P = .001), cardiac diseases (P = .005), diabetes mellitus (P = .03), allograft rejection (P = .001), CMV infection (P = .001), and severe lymphopenia (P = .001) were significantly higher in cases. In the logistic regression model, CMV infection (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 2.0-10.5]) and allograft rejection (aOR, 3.0 [95% CI, 1.5-6.1]) significantly increased the likelihood of PCP. CONCLUSIONS: PCP was mostly a late-onset disease occurring after complete course of prophylaxis, particularly among patients with CMV infection or allograft rejection. PCP is associated with significant allograft loss. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PCP.

The impact of repeated mismatches in kidney transplantations performed after nonrenal solid organ transplantation.

The aim of this study was to determine whether kidney transplantations performed after previous nonrenal solid organ transplants are associated with worse graft survival when there are repeated HLA mismatches (RMM) with the previous donor(s). We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients. Our cohort comprised 6624 kidney transplantations performed between January 1, 1990 and January 1, 2015. All patients had previously received 1 or more nonrenal solid organ transplants. RMM were observed in 35.3% of kidney transplantations and 3012 grafts were lost over a median follow-up of 5.4 years. In multivariate Cox regression analyses, we found no association between overall graft survival and either RMM in class 1 (hazard ratio [HR]: 0.97, 95% confidence interval [CI] 0.89-1.07) or class 2 (HR: 0.95, 95% CI 0.85-1.06). Results were similar for the associations between RMM, death-censored graft survival, and patient survival. Our results suggest that the presence of RMM with previous donor(s) does not have an important impact on allograft survival in kidney transplant recipients who have previously received a nonrenal solid organ transplant.

Anti-LG3 Antibodies Aggravate Renal Ischemia-Reperfusion Injury and Long-Term Renal Allograft Dysfunction.

Pretransplant autoantibodies to LG3 and angiotensin II type 1 receptors (AT1R) are associated with acute rejection in kidney transplant recipients, whereas antivimentin autoantibodies participate in heart transplant rejection. Ischemia-reperfusion injury (IRI) can modify self-antigenic targets. We hypothesized that ischemia-reperfusion creates permissive conditions for autoantibodies to interact with their antigenic targets and leads to enhanced renal damage and dysfunction. In 172 kidney transplant recipients, we found that pretransplant anti-LG3 antibodies were associated with an increased risk of delayed graft function (DGF). Pretransplant anti-LG3 antibodies are inversely associated with graft function at 1 year after transplantation in patients who experienced DGF, independent of rejection. Pretransplant anti-AT1R and antivimentin were not associated with DGF or its functional outcome. In a model of renal IRI in mice, passive transfer of anti-LG3 IgG led to enhanced dysfunction and microvascular injury compared with passive transfer with control IgG. Passive transfer of anti-LG3 antibodies also favored intrarenal microvascular complement activation, microvascular rarefaction and fibrosis after IRI. Our results suggest that anti-LG3 antibodies are novel aggravating factors for renal IRI. These results provide novel insights into the pathways that modulate the severity of renal injury at the time of transplantation and their impact on long-term outcomes.

Antiperlecan antibodies are novel accelerators of immune-mediated vascular injury.

Acute vascular rejection (AVR) is characterized by immune-mediated vascular injury and heightened endothelial cell (EC) apoptosis. We reported previously that apoptotic ECs release a bioactive C-terminal fragment of perlecan referred to as LG3. Here, we tested the possibility that LG3 behaves as a neoantigen, fuelling the production of anti-LG3 antibodies of potential importance in regulating allograft vascular injury. We performed a case-control study in which we compared anti-LG3 IgG titers in kidney transplant recipients with AVR (n=15) versus those with acute tubulo-interstitial rejection (ATIR) (n=15) or stable graft function (n=30). Patients who experienced AVR had elevated anti-LG3 titers pre and posttransplantation compared to subjects with ATIR or stable graft function (p<0.05 for both mediators). Elevated pretransplant anti-LG3 titers (OR: 4.62, 95% CI: 1.08-19.72) and pretransplant donor-specific antibodies (DSA) (OR 4.79, 95% CI: 1.03-22.19) were both independently associated with AVR. To address the functional role of anti-LG3 antibodies in AVR, we turned to passive transfer of anti-LG3 antibodies in an animal model of vascular rejection based on orthotopic aortic transplantation between fully MHC-mismatched mice. Neointima formation, C4d deposition and allograft inflammation were significantly increased in recipients of an ischemic aortic allograft passively transferred with anti-LG3 antibodies. Collectively, these data identify anti-LG3 antibodies as novel accelerators of immune-mediated vascular injury and obliterative remodeling.

Disparities in Deceased Donor Kidney Offer Acceptance: A Survey of Canadian Transplant Nephrologists, General Surgeons and Urologists.

Background: Significant variability in organ acceptance thresholds have been demonstrated across the United States, but data regarding the rate and rationale for kidney donor organ decline in Canada are lacking. Objective: To examine decision making regarding deceased kidney donor acceptance and non-acceptance in a population of Canadian transplant professionals. Design: A survey study of theoretical deceased donor kidney cases of increasing complexity. Setting: Canadian transplant nephrologists, urologists, and surgeons making donor call decisions responding to an electronic survey between July 22 and October 4, 2022. Participants: Invitations to participate were distributed to 179 Canadian transplant nephrologists, surgeons, and urologists through e-mail. Participants were identified by contacting each transplant program and requesting a list of physicians who take donor call. Measurements: Survey respondents were asked whether they would accept or decline a given donor, assuming there was a suitable recipient. They were also asked to cite reasons for donor non-acceptance. Methods: Donor scenario-specific acceptance rates (total acceptance divided by total number of respondents for a given scenario and overall) and reasons for decline were determined and presented as a percentage of the total cases declined. Results: In all, 72 respondents from 7 provinces completed at least one question of the survey, with considerable variability between acceptance rates for centers; the most conservative center declined 60.9% of donor cases, whereas the most aggressive center declined only 28.1%, P-value < .001. There was an increased risk of non-acceptance with advancing age, donation after cardiac death, acute kidney injury, chronic kidney disease, and comorbidities. Limitations: As with any survey, there is the potential for participation bias. In addition, this study examines donor characteristics in isolation, however, asks respondent to assume there is a suitable candidate available. In reality, whenever donor quality is considered, it should be considered in the context of the intended recipient. Conclusion: In a survey of increasingly medically complex deceased kidney donor cases, there was significant variability in donor decline among Canadian transplant specialists. Given relatively high rates of donor decline and apparent heterogeneity in acceptance decisions, Canadian transplant specialists may benefit from additional education regarding the benefits achieved from even medically complex kidney donors for appropriate candidates relative to remaining on dialysis on the transplant waitlist.

Contexte: Une importante variabilité a été observée aux États-Unis dans le seuil d'acceptation des organes. Au Canada, on manque de données sur le taux de refus des donneurs de reins et sur les raisons qui expliquent ce refus. Objectifs: Examiner la prise de décision quant à l'acceptation ou non d'un donneur de rein décédé dans une population de professionnels de la transplantation canadiens. Conception: Un sondage exposant des cas théoriques de plus en plus complexes de donneurs de reins décédés. Cadre: Des néphrologues, urologues et chirurgiens canadiens spécialisés en transplantation qui prennent des décisions relatives au don d'organes ont été invités à répondre à un sondage électronique entre le 22 juillet et le 4 octobre 2022. Participants: L'invitation à participer a été distribuée par courriel à 179 néphrologues, chirurgiens et urologues canadiens spécialisés en transplantation. Les participants ont été identifiés en communiquant avec chaque program de transplantation pour obtenir une liste des médecins recevant des offres d'organes. Mesures: Les répondants devaient indiquer s'ils accepteraient ou refuseraient un donneur donné, en supposant qu'un receveur approprié existait. Ils étaient également invités à citer les raisons justifiant le refus d'un donneur. Méthodologie: Les taux d'acceptation par scénario (acceptation totale divisée par le nombre total de répondants pour un scénario donné, et pour l'ensemble) et les raisons du refus ont été déterminés et présentés sous forme de pourcentage du nombre total de cas refusés. Résultats: En tout, 72 professionnels issus de 7 provinces avaient répondu à au moins une question du sondage. On a observé une grande variabilité du taux d'acceptation entre les différents centers; le plus conservateur avait refusé 60,9 % des donneurs présentés alors que le plus entreprenant n'avait refusé que de 28,1 % des cas (p < 0,001). Les donneurs d'âge avancé, ceux décédés d'un problème cardiaque et ceux qui souffraient d'insuffisance rénale aiguë, d'insuffisance rénale chronique et de comorbidités étaient plus susceptibles d'être refusés. Limites: Comme pour toute étude sous forme de sondage, celle-ci comporte un possible biais de participation. Cette étude examine les caractéristiques du donneur de manière isolée, mais demande aux répondants de supposer qu'un candidat approprié existe. Dans la réalité, chaque fois que la qualité d'un donneur est évaluée, elle doit être prise en compte dans le contexte du receveur visé. Conclusion: Dans cette étude présentant des cas théoriques de complexité croissante sur le plan médical de donneurs de reins décédés, une importante variabilité a été observée quant au refus des donneurs par les spécialistes de la transplantation canadiens. Les taux relativement élevés de refus et l'apparente hétérogénéité des décisions liées à l'acceptation justifient plus d'éducation auprès des spécialistes de la transplantation canadiens; notamment sur les avantages pour un candidat approprié de recevoir un organe, même si ce dernier provient d'un cas médicalement complexe, par rapport au fait de rester en dialyze sur la liste d'attente pour une transplantation.

Mechanisms responsible for endothelial dysfunction induced by fasting hyperhomocystinemia in normotensive subjects and patients with essential hypertension.

OBJECTIVES: We sought to evaluate whether fasting hyperhomocystinemia reduces endothelial function by oxidative stress in normotensive subjects and hypertensive patients. BACKGROUND: Subjects with hyperhomocystinemia have endothelial dysfunction. METHODS: In 23 normotensive subjects and 28 hypertensive patients, classified into normohomocystinemic and hyperhomocystinemic groups according to homocysteine plasma levels (< 8.7 and >14.6 micromol/l, respectively), we studied forearm blood flow changes (strain-gauge plethysmography) induced by intrabrachial administration of acetylcholine (0.15 to 15 microg/100 ml tissue per min) or sodium nitroprusside (1 to 4 microg/100 ml per min), an endothelium-dependent and -independent vasodilator, respectively. Acetylcholine was repeated with N(G)-monomethyl-L-arginine (L-NMMA; 100 microg/100 ml per min), vitamin C (8 mg/100 ml per min) and L-NMMA plus vitamin C. RESULTS: Normotensive hyperhomocystinemic patients showed a blunted response to acetylcholine and a lower inhibiting effect of L-NMMA on acetylcholine, as compared with normohomocystinemic patients. Although vitamin C was ineffective in normohomocystinemic subjects, it increased the response to acetylcholine and restored the inhibiting effect of L-NMMA on acetylcholine in hyperhomocystinemic patients. Hypertensive hyperhomocystinemic patients showed a reduced response to acetylcholine, as compared with normohomocystinemic subjects. In both subgroups, L-NMMA failed to blunt the response to acetylcholine. The potentiating effect of vitamin C on acetylcholine was greater in hyperhomocystinemic patients than in normohomocystinemic subjects, although it restored the inhibitory effect of L-NMMA on acetylcholine-induced vasodilation to the same extent in both groups. Hyperhomocystinemia did not change the response to sodium nitroprusside. CONCLUSIONS: In normotensive subjects and hypertensive patients, hyperhomocystinemia impairs endothelium-dependent vasodilation. It could be related to oxidant activity.

The set point of parathyroid hormone stimulation by calcium is normal in progressive renal failure.

An increased set point of PTH stimulation by ionized calcium (Ca++) has been observed in renal failure patients with severe secondary hyperparathyroidism. The extension of this concept to all renal failure patients has remained problematic, even if it could explain elevated PTH levels in the absence of other biochemical abnormalities. We were particularly interested in seeing whether the concept could fit patients with progressive renal failure (PRF). To achieve this, we studied 26 normals (N), 9 patients with PRF, and 12 hemodialyzed patients (HD) in the basal state and during parathyroid function tests. The latter two groups were studied at the end of winter and end of summer, respectively. Patients with PRF had normal levels of Ca++, PO4, and 1,25(OH)2D, and they had low-normal concentrations of 25(OH)D; their basal I- and C-PTH levels were 3- and 4-fold higher than N, as were their creatinine levels. HD had significantly lower levels of Ca++ and 1,25(OH)2D, and they had higher levels of phosphate, creatinine, I-PTH, and C-PTH than N or PRF. Stimulated levels of I-PTH were similar in N (13.6 +/- 4.3 pmol/L) and PFR (18 +/- 3.3 pmol/L) and elevated in HD (37.1 +/- 28.7 pmol/L; P < 0.001 vs. N, and P < 0.05 vs. PRF). Nonsuppressible I-PTH was increased 2-fold in PRF (N = 0.64 +/- 0.19 vs. PRF = 1.28 +/- 0.46 pmol/L; P < 0.01) and 6-fold in HD (3.95 +/- 2.85 pmol/L; P < 0.001 vs. others). But the set point of I-PTH stimulation by Ca++ was normal in PRF (N = 1.18 +/- 0.03 vs. PRF = 1.20 +/- 0.04 mmol/L; not significant) and decreased in HD (1.09 +/- 0.04 mmol/L; P < 0.001 vs. others). Similar results were obtained with the set point of C-PTH and of the C-PTH/I-PTH ratio. A positive correlation was observed between serum Ca++ concentration and the set point value when all three populations were analyzed together (r = 0.759, n = 47, P < 0.0001). These results indicate that the set point of PTH stimulation is normal in PRF and decreased in hypocalcemic HD. The set point seems to adjust to the ambient Ca++ concentration of the patients, by mechanisms yet to be elucidated. This does not suggest participation of this factor to the genesis of the secondary hyperparathyroidism of PRF.

Analytic approximation of the log-signal and log-variance functions of x-ray imaging systems, with application to dual-energy imaging.

In the analysis of x-ray system performance, the log-signal function, or negative logarithm of the relative detector signal, and the analogously defined log-variance function, are of central importance. These are smooth, monotonic functions of object thickness, which are nonlinear for nonmonoenergetic x-ray source spectra. If we assume a dual-energy decomposition of the object into two basis materials, then they can be written as analytic functions f(x,y) and f*(x,y), respectively, of the component thicknesses (x,y) of the object. In this paper, we analytically develop the Taylor series of these functions, prove that they converge everywhere, and parametrize their coefficients via suitable central spectral moments of the basis-material attenuation coefficients. We then show how the lower-order moments can be used to construct, in closed form, smooth, monotonic, second-order (conic) surface functions which closely approximate f(x,y) and f*(x,y) over the entire feasible domain. A simplified construction, based on using appropriate asymptotic values of the basis-material attenuation coefficients to match the asymptotic behavior of these functions, is also given. The inclusion of image components with K-edge absorption spectra, such as iodine, is done without effort. Extension of the results to the construction of similar (virtually exact) third-order (cubic) surface approximations is straightforward. As an illustration of the broad applicability of this approach, we extend our analysis to the construction of similar approximations to the inverse (decomposition) functions for an arbitrary dual-energy system, and investigate their numerical accuracy for a model dual-kVp system. We conclude that this extended analysis provides an accurate description of the system behavior in terms of a small number of physically meaningful parameters. This parametrization permits greater physical insight into the system behavior, while at the same time simplifying its mathematical description, and similarly facilitates the analysis of various measures of imaging performance via either analytic or numerical methods.

Theoretical optimization of a split septaless xenon ionization detector for dual-energy chest radiography.

It is proposed that digital scanned projection radiography of the chest be performed by using an energy-sensitive septaless xenon ionization detector (SXID) to obtain dual-energy images. The proposed detector is composed of a front region, sensitive to low-energy x rays, and a rear region, sensitive to high-energy x rays, separated by a suitable filter layer. We have developed a simple, precise theoretical formulation for dual-energy optimization, and applied it to the split SXID. We describe the variation of optimum detector performance with source kilovoltage and filtration (material and thickness), and hence heat loading, under conditions of constant exposure and constant dose. We estimate dose as the average absorbed dose to an equivalent water layer of suitable thickness, assuming slab geometry, so that the calculation is as simple as that for exposure.

An accurate method for direct dual-energy calibration and decomposition.

We propose the use of conic and cubic surface equations (surfaces of second and third order) to directly approximate the dual-energy equations (the integral equations for the dual-energy log-signal functions, i.e., the negative logarithms of the relative detector signals, considered as functions of the basis-material component thicknesses of the object) and especially their inverses. These types of surface equations require a minimum number of calibration points, and their solutions are smooth, monotonic functions with the correct linear asymptotic behavior. The accuracy of this method is investigated and compared to that of conventional polynomial approximations, both for simulated and real calibration data, taken from two split-detector systems. These systems provide a more stringent test of our method than comparable dual-kVp systems, due to the greater nonlinearity of their log-signal and inverse functions. For these systems, we show that direct approximation of the inverse dual-energy equations using the simple eight-term rational form of the conic surface equation provides an extremely fast decomposition algorithm, which is accurate, robust in the presence of noise, and which can be calibrated with as few as 9 calibration points, or robustly calibrated, with a built-in accuracy check, using only 16 calibration points. Also, we show that extreme accuracy of approximation (to within less than 10(-6) in log-signal and 1 micron in material thickness) is theoretically attainable using the eighteen-term form of the cubic surface equation, which has a closed-form analytic solution. Finally, we consider the effects of noise on calibration accuracy, and derive simple formulas which relate the true and apparent root-mean-square (rms) accuracies. These formulas then allow the comparison of the true rms calibration accuracies of various surface approximations, considered as functions of the total calibration heat loading of the x-ray tube.

Automatic needle segmentation in three-dimensional ultrasound images using two orthogonal two-dimensional image projections.

In this paper, we describe an algorithm to segment a needle from a three-dimensional (3D) ultrasound image by using two orthogonal two-dimensional (2D) image projections. Not only is the needle more conspicuous in a projected (volume-rendered) image, but its direction in 3D lies in the plane defined by the projection direction and the needle direction in the projected 2D image. Hence, using two such projections, the 3D vector describing the needle direction lies along the intersection of the two corresponding planes. Thus, the task of 3D needle segmentation is reduced to two 2D needle segmentations. For improved accuracy and robustness, we use orthogonal projection directions (both orthogonal to a given a priori estimate of the needle direction), and use volume cropping and Gaussian transfer functions to remove complex background from the 2D projection images. To evaluate our algorithm, we tested it with 3D ultrasound images of agar and turkey breast phantoms. Using a 500 MHz personal computer equipped with a commercial volume-rendering card, we found that our 3D needle segmentation algorithm performed in near real time (about 10 fps) with a root-mean-square accuracy in needle length and endpoint coordinates of better than 0.8 mm, and about 0.5 mm on average, for needles lengths in the 3D image from 4.0 mm to 36.7 mm.

An in-line optical image translator with applications in x-ray videography.

Many applications in radiography require, or would benefit from, the ability to translate, i.e. move, an optical image in the detector plane. In this paper, we describe the design and characterization of a prism-based optical image translator for insertion into existing XRII-video imaging systems. A pair of prisms rotatable about the optical axis form a very compact in-line optical image translator for installation in the parallel light path between an x-ray image intensifier and its video camera. Rotation of the prisms translates the XRII optical image on the camera target. With the addition of x-ray and light collimators to limit the image to a single video line, x-ray streak images may be acquired. By rotating an object in the x-ray beam during a streak, a complete computed tomography (CT) data set may be acquired. This image translator can translate an image anywhere in the focal plane of a 50-mm-output lens within a 40-mm-diam circle. The prisms have an aperture of 50 mm, permitting an optical speed of F/2 with a 50-mm output lens. The design is insensitive to angular alignment errors. This image translator is achromatic, since the spectral width of the output phosphorus of image intensifiers is sufficient to introduce blurring in a nonacrhomatic design. A prism-based image translator introduces image distortion, since the prisms do not operate at minimum deviation. The distortion is less than 4% over all parts of a typical detector area, and less than 1% in the central region of the image.(ABSTRACT TRUNCATED AT 250 WORDS)

Semiautomatic three-dimensional segmentation of the prostate using two-dimensional ultrasound images.

In this paper, we report on two methods for semiautomatic three-dimensional (3-D) prostate boundary segmentation using 2-D ultrasound images. For each method, a 3-D ultrasound prostate image was sliced into the series of contiguous 2-D images, either in a parallel manner, with a uniform slice spacing of 1 mm, or in a rotational manner, about an axis approximately through the center of the prostate, with a uniform angular spacing of 5 degrees. The segmentation process was initiated by manually placing four points on the boundary of a selected slice, from which an initial prostate boundary was determined. This initial boundary was refined using the Discrete Dynamic Contour until it fit the actual prostate boundary. The remaining slices were then segmented by iteratively propagating this result to an adjacent slice and repeating the refinement, pausing the process when necessary to manually edit the boundary. The two methods were tested with six 3-D prostate images. The results showed that the parallel and rotational methods had mean editing rates of 20% and 14%, and mean (mean absolute) volume errors of -5.4% (6.5%) and -1.7% (3.1%), respectively. Based on these results, as well as the relative difficulty in editing, we conclude that the rotational segmentation method is superior.

Experimental and theoretical x-ray imaging performance comparison of iodine and lanthanide contrast agents.

Contrast agents based on the lanthanide elements gadolinium and holmium have recently been developed for magnetic resonance imaging (MRI). Because of the increased atomic number of these elements relative to iodine, these new compounds, used as x-ray contrast agents, may yield higher radiographic contrast, and hence improved x-ray image quality, relative to conventional iodinated compounds, for clinically useful x-ray spectra. This possibility has been investigated, in independent experimental and theoretical studies, for two x-ray imaging systems: a digital radiographic system, using an x-ray image intensifier (XRII) and charge-coupled device (CCD) detector; and a conventional screen/film system, using a Lanex Regular screen. Iodine, gadolinium, and holmium contrast agents were investigated over a wide range of concentration-thickness products (0.1-0.6 M cm) and diagnostic x-ray spectra (60-120 kVp). A simple theoretical model of x-ray detector response predicts the experimental radiographic contrast measurements with a mean absolute error of 8.0% for the XRII/CCD system and 5.9% for the screen/film system, and shows that the radiographic contrast for these two systems is representative of all XRII and screen/film systems. An index of image quality is defined, and its dependence on radiographic contrast, x-ray fluence per unit dose, and detective quantum efficiency (DQE) is shown. Theoretical values of the index, predicted by our model, are then used to compare the performance of the three contrast agents for the two systems investigated. In general, iodine performance decreases steadily with increasing kVp, gadolinium performance has a broad maximum near 85 kVp, and gadolinium outperforms holmium. Gadolinium outperforms iodine for spectra above (and vice versa below) about 72 kVp, depending slightly on spectrum filtration, object thickness, and detector type. Thus, raising the kVp to shorten exposure times or reduce x-ray tube heat loading results in a loss of image quality with iodine, but not with gadolinium. Similarly, beam-hardening artifacts in performing video densitometry with iodine would be reduced with gadolinium. Gadolinium-based contrast agents are thus shown to offer several practical advantages over conventional iodinated contrast agents.

Analysis of geometrical distortion and statistical variance in length, area, and volume in a linearly scanned 3-D ultrasound image.

A linearly scanned three-dimensional (3-D) ultrasound imaging system is considered. The transducer array is initially oriented along the x axis and aimed in the y direction. After being tilted by an angle theta about the x axis, and then swiveled by an angle phi about the y axis, it is translated in the z direction, in steps of size d, to acquire a series of parallel two-dimendional (2-D) images. From these, the 3-D image is reconstructed, using the nominal values of the parameters (phi, theta, d). Thus, any systematic or random errors in these, relative to their actual values (phi0, theta0, d0), will respectively cause distortions or variances in length, area, and volume in the reconstructed 3-D image, relative to the 3-D object. Here, we analyze these effects. Compact linear approximations are derived for the relative distortions as functions of the parameter errors, and hence, for the relative variances as functions of the parameter variances. Also, exact matrix formulas for the relative distortions are derived for arbitrary values of (phi, theta, d) and (phi0, theta0, d0). These were numerically compared to the linear approximations and to measurements from simulated 3-D images of a cubical object and real 3-D images of a wire phantom. In every case tested, the theory was confirmed within experimental error (0.5%).

Three-dimensional ultrasound imaging.

Ultrasound is an inexpensive and widely used imaging modality for the diagnosis and staging of a number of diseases. In the past two decades, it has benefited from major advances in technology and has become an indispensable imaging modality, due to its flexibility and non-invasive character. In the last decade, research investigators and commercial companies have further advanced ultrasound imaging with the development of 3D ultrasound. This new imaging approach is rapidly achieving widespread use with numerous applications. The major reason for the increase in the use of 3D ultrasound is related to the limitations of 2D viewing of 3D anatomy, using conventional ultrasound. This occurs because: (a) Conventional ultrasound images are 2D, yet the anatomy is 3D, hence the diagnostician must integrate multiple images in his mind. This practice is inefficient, and may lead to variability and incorrect diagnoses. (b) The 2D ultrasound image represents a thin plane at some arbitrary angle in the body. It is difficult to localize the image plane and reproduce it at a later time for follow-up studies. In this review article we describe how 3D ultrasound imaging overcomes these limitations. Specifically, we describe the developments of a number of 3D ultrasound imaging systems using mechanical, free-hand and 2D array scanning techniques. Reconstruction and viewing methods of the 3D images are described with specific examples. Since 3D ultrasound is used to quantify the volume of organs and pathology, the sources of errors in the reconstruction techniques as well as formulae relating design specification to geometric errors are provided. Finally, methods to measure organ volume from the 3D ultrasound images and sources of errors are described.

A three-dimensional ultrasound prostate imaging system.

We have developed a three-dimensional (3D) transrectal ultrasound imaging system, based on using a motorized 5 MHz transducer assembly, rotated under microcomputer control, to collect a series of 100 two-dimensional (2D) images, digitized by a video frame-grabber. These are then reconstructed into a 3D image on a computer workstation, permitting the prostate anatomy to be visualized in three dimensions, and distance and volume measurements to be performed. The accuracy of the distance measurements was assessed with a string test phantom, and that of the volume measurements with balloons of known sizes. Also, the resolution degradation engendered by the reconstruction algorithm was assessed by comparing the full-width at half-maximum (FWHM) of string cross-sectional images in the 3D image to their 2D counterparts. The results show that distance and volume measurements are both accurate to about +/- 1%, and that the reconstruction algorithm increases the mean FWHM by 8 +/- 3% axially and 3 +/- 3% laterally.

Analysis of linear, area and volume distortion in 3D ultrasound imaging.

We have developed a three-dimensional (3D) ultrasound imaging system that uses a side-firing probe, axially rotated under computer control, to acquire a series of 2D images, from which the 3D image is reconstructed. For an undistorted reconstruction, the inner radius R0 of the 2D images and the total scanning angle theta must be known accurately. Here, we describe (a) a theoretical analysis of the relative distortion in image shape, length, area, and volume due to an error delta R in R0 or delta theta in theta; (b) measurements of these in simulated and real 3D images; and (c) a method to calibrate R0, theta, and image scale accurately. Theoretically, all four relative distortions vary as P delta R/R + Q delta theta/theta, where magnitude of P < or = 1, magnitude of Q < or = 1, and R is the average distance of the object from the axis. In every case, the simple theoretical formulas for P and Q agree with image measurements to within the measurement uncertainty.

A real vessel phantom for flow imaging: 3-D Doppler ultrasound of steady flow.

Vascular phantoms are used to assess the capabilities of various imaging techniques, such as x-ray CT and angiography, and B-mode, power Doppler, and colour Doppler ultrasound (US). They should, therefore, accurately mimic the vasculature, blood, and surrounding tissue, in regard to both imaging properties and vessel geometry. In the past, a variety of walled and wall-less vessel models have been used. However, these models only approximate the true vessel geometry, and generally lack pathologic features such as plaques or calcifications. To amend these deficiencies, we have developed a real vessel phantom for US and x-ray studies, which comprises a fixed human vessel specimen, cannulated onto two acrylic tubes, and embedded in agar in an acrylic box. Earlier, we demonstrated a good overall correlation between x-ray angiography, CT, and 3-D B-mode US images of this phantom. Here, we extend its use to flow imaging with 3-D power and 3-D colour Doppler US.

Intra- and inter-observer variability and reliability of prostate volume measurement via two-dimensional and three-dimensional ultrasound imaging.

We describe the results of a study to evaluate the intra- and inter-observer variability and reliability of prostate volume measurements made from transrectal ultrasound (TRUS) images, using either the (optimal) height-width-length (HWL) method (V = pi/6 HWL) with two-dimensional (2D) TRUS images (obtained as cross-sections of three-dimensional [3D] TRUS images) or manual planimetry of 3D TRUS images (the 3D US method). In this study, eight observers measured 15 prostate images, twice via each method, and an analysis of variance (ANOVA) was performed. This analysis shows that, with the 3D US method, intra-observer prostate volume estimates have 5.1% variability and 99% reliability, and inter-observer estimates have 11.4% variability and 96% reliability. With the HWL method, intra-observer estimates have 15.5% variability and 93% reliability, and inter-observer estimates have 21.9% variability and 87% reliability. Thus, in vivo prostate volume estimates from manual planimetry of 3D TRUS images have much lower variability and higher reliability than HWL estimates from 2D TRUS images.