Influence of image artifacts on image-based computer simulations of the cardiac electrophysiology.

Myocardial infarct patients have an increased risk of scar-based ventricular tachycardia. Late gadolinium enhanced magnetic resonance (MR) imaging provides the geometric extent of myocardial infarct. Computational electrophysiological models based on such images can provide a personalized prediction of the patient's tachycardia risk. In this work, the effect of respiratory slice alignment image artifacts on image-based electrophysiological simulations is investigated in two series of models. For the first series, a clinical MR image is used in which slice translations are applied to artificially induce and correct for slice misalignment. For the second series, computer simulated MR images with and without slice misalignments are created using a mechanistic anatomical phantom of the torso. From those images, personalized models are created in which electrical stimuli are applied in an attempt to induce tachycardia. The response of slice-aligned and slice-misaligned models to different interval stimuli is used to assess tachycardia risk. The presented results indicate that slice misalignments affect image-based simulation outcomes. The extent to which the assessed risk is affected is found to depend upon the geometry of the infarct area. The number of unidirectional block tachycardias varied from 1 to 3 inducible patterns depending on slice misalignment severity and, along with it, the number of tachycardia inducing stimuli locations varied from 2 to 4 from 6 different locations. For tachycardias sustained by conducting channels through the scar core, no new patterns are induced by altering the slice alignment in the corresponding image. However, it affected the assessed risk as tachycardia inducing stimuli locations varied from 1 to 5 from the 6 stimuli locations. In addition, if the conducting channel is not maintained in the image due to slice misalignments, the channel-dependent tachycardia is not inducible anymore in the image-based model.

Prostate cancer localization by novel magnetic resonance dispersion imaging.

Diagnosis and focal treatment of prostate cancer, the most prevalent form of cancer in men, is hampered by the limits of current clinical imaging. Angiogenesis imaging is a promising option for detection and localization of prostate cancer. It can be imaged by dynamic contrast-enhanced (DCE) MRI, assessing microvascular permeability as an indicator for angiogenesis. However, information on microvascular architecture changes associated with angiogenesis is not available. This paper presents a new model enabling the combined assessment of microvascular permeability and architecture. After the intravenous injection of a gadolinium-chelate bolus, time-concentration curves (TCCs) are measured by DCE-MRI at each voxel. According to the convective dispersion equation, the microvascular architecture is reflected in the dispersion coefficient. A solution of this equation is therefore proposed to represent the intravascular blood plasma compartment in the Tofts model. Fitting the resulting model to TCCs measured at each voxel leads to the simultaneous generation of a dispersion and a permeability map. Measurement of an arterial input function is no longer required. Preliminary validation was performed by spatial comparison with the histological results in seven patients referred for radical prostatectomy. Cancer localization by the obtained dispersion maps provided an area under the receiver operating characteristic curve equal to 0.91. None of the standard DCE-MRI parametric maps could outperform this result, motivating towards an extended validation of the method, also aimed at investigating other forms of cancer with pronounced angiogenic development.

Assisting vascular access surgery planning for hemodialysis by using MR, image segmentation techniques, and computer simulations.

The surgical creation of a vascular access, used for hemodialysis treatment of renal patients, has considerable complication rates (30-50 %). Image-based computational modeling might assist the surgeon in planning by enhanced analysis of preoperative hemodynamics, and in the future might serve as platform for outcome prediction. The objective of this study is to investigate preoperative personalization of the computer model using magnetic resonance (MR). MR-angiography and MR-flow data were obtained for eight patients and eight volunteers. Blood vessels were extracted for model input by a segmentation algorithm. Windkessel elements were added at the ends to represent the peripheral beds. Monte Carlo-based calibration was used to estimate the most influential non-measurable parameters. The predicted flow waveforms were compared with the MR-flow measurements for framework evaluation. The vasculature of all subjects were segmented in on average <5 min. The Monte Carlo-calibrated simulations showed a deviation between measured and simulated flow waveforms of 9 and 10 % for volunteers and patients, respectively. The presented method accurately mimics the preoperative hemodynamic state. Furthermore, the surgeon can interactively explore the hemodynamics at any vascular tree position. This integration of measurements in a modeling approach can provide the surgeon with additional information for preoperative planning.

Quantitative analysis of transmural gradients in myocardial perfusion magnetic resonance images.

Conventional quantitative assessments of myocardial perfusion analyze the temporal relation between the arterial input function and the myocardial signal intensity curves, thereby neglecting the important spatial relation between the myocardial signal intensity curves. The new method presented in this article enables characterization of sub-endocardial to sub-epicardial gradients in myocardial perfusion based on a two dimensional, "gradientogram" representation, which displays the evolution of the transmural gradient in myocardial contrast uptake over time in all circumferential positions of the acquired images. Moreover, based on segmentation in these gradientograms, several new measurements that characterize transmural myocardial perfusion distribution over time are defined. In application to clinical image data, the new two-dimensional representations, as well as the newly defined measurements revealed a clear distinction between normal perfusion and inducible ischaemia. Thus, the new measurements may serve as diagnostic markers for the detection and characterization of epicardial coronary and microvascular disease.

Predicting patient-specific expansion of abdominal aortic aneurysms.

OBJECTIVE: Local anatomy and the patient's risk profile independently affect the expansion rate of an abdominal aortic aneurysm. We describe a hybrid method that combines finite element modelling and statistical methods to predict patient-specific aneurysm expansion. METHODS: The 3-D geometry of the aneurysm was imaged with computed tomography. We used finite element methods to calculate wall stress and aneurysm expansion. Expansion rate was adjusted by risk factors obtained from a database of 80 patients. Aneurysm diameters predicted with and without the risk profiles were compared with diameters measured with ultrasound for 11 patients. RESULTS: For this specific group of patients, local anatomy contributed 62% and the risk profile 38% to the aneurysmal expansion rate. Predictions with risk profiles resulted in smaller root mean square errors than predictions without risk profiles (2.9 vs. 4.0 mm, p < 0.01). CONCLUSIONS: This hybrid approach predicted aneurysmal expansion for a period of 30 months with high accuracy.

The influence of wall stress on AAA growth and biomarkers.

OBJECTIVES: This study investigated the relation between abdominal aortic aneurysm (AAA) wall stress, AAA growth rate and biomarker concentrations. With increasing wall stress, more damage may be caused to the AAA wall, possibly leading to progression of the aneurysm and reflection in up- or downregulation of specific circulating biomarkers. Levels of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1, C-reactive protein and alpha 1-antitrypsin were therefore evaluated. METHODS: Thirty-seven patients (maximum AAA diameter 41-55mm) with two, three or four consecutive computed tomography angiography (CTA) scans were prospectively included. Diameter growth rate in mm/year was determined between each pair of two sequential CTA scans. AAA wall stress was computed by finite element analysis, based on the first of the two sequential CTA scans only (n=69 pairs). Biomarker information was determined in 46 measurements in 18 patients. The relation between AAA diameter and wall stress was determined and the AAA's were divided into three equally sized groups (relative low, medium and high stress). Growth rate and biomarker concentrations were compared between these groups. Additionally, correlation coefficients were computed between absolute wall stress, AAA growth and biomarker concentrations. RESULTS: A relative low AAA wall stress was associated with a lower aneurysm growth rate. Growth rate was also positively related to MMP-9 plasma concentration (r=0.32). The average MMP-9 and CRP concentrations increased with increasing degrees of relative wall stress, although the absolute and relative wall stress did not correlate with any of the biomarkers. CONCLUSION: Although lower relative wall stress was associated to a lower AAA growth rate, no relation was found between biomarker concentrations and wall stress. Future research may focus on more and extensive biomarker measurements in relation to AAA wall stress.

Importance of initial stress for abdominal aortic aneurysm wall motion: dynamic MRI validated finite element analysis.

Currently the transverse diameter is the primary decision criterion to assess rupture risk in patients with an abdominal aortic aneurysm (AAA). To obtain a measure for more patient-specific risk assessment, aneurysm wall stress, calculated using finite element analysis (FEA), has been evaluated in literature. In many cases, initial stress, present in the AAA wall during image acquisition, is not taken into account. In the current study the effect of initial stress incorporation (ISI) is determined by directly comparing wall displacements extracted from FEA and dynamic MRI. Ten patients with an aneurysm diameter >5.5 cm were scanned with cardiac triggered MRI. Semi-automatic segmentation of the AAA was performed on the diastolic phase. The segmented in-slice contours were propagated through the remaining cardiac phases using an active contour model as to track wall displacements on MRI. Consequently, FEA with and without ISI (no-ISI) was performed using the diastolic geometry with simultaneously measured intra-aneurysm pressure values as boundary condition. Contours extracted from FEA were compared with MRI contours at corresponding cardiac phases by distance and relative area differences. The wall displacements from FEA with ISI show significant better correspondence with wall motion from MRI data in comparison with the no-ISI FEA (deviation in wall displacement 1.7% vs. 12.4%; p<0.001). Based on these results it can be concluded that incorporation of initial stress significantly improves wall displacement accuracy of FEA and therefore it should be incorporated in future analyses.

Initial stress and nonlinear material behavior in patient-specific AAA wall stress analysis.

Rupture risk estimation of abdominal aortic aneurysms (AAA) is currently based on the maximum diameter of the AAA. A more critical approach is based on AAA wall stress analysis. For that, in most cases, the AAA geometry is obtained from CT-data and treated as a stress free geometry. However, during CT imaging, the AAA is subjected to a time-averaged blood pressure and is therefore not stress free. The aim of this study is to evaluate the effect of neglecting these initial stresses (IS) on the patient-specific AAA wall stress as computed by finite element analysis. Additionally, the contribution of the nonlinear material behavior of the AAA wall is evaluated. Thirty patients with maximum AAA diameters below the current surgery criterion were scanned with contrast-enhanced CT and the AAA's were segmented from the image data. The mean arterial blood pressure (MAP) was measured immediately after the CT-scan and used to compute the IS corresponding with the CT geometry and MAP. Comparisons were made between wall stress obtained with and without IS and with linear and nonlinear material properties. On average, AAA wall stresses as computed with IS were higher than without IS. This was also the case for the stresses computed with the nonlinear material model compared to the linear material model. However, omitting initial stress and material nonlinearity in AAA wall stress computations leads to different effects in the resulting wall stress for each AAA. Therefore, provided that other assumptions made are not predominant, IS cannot be discarded and a nonlinear material model should be used in future patient-specific AAA wall stress analyses.

Patient-specific AAA wall stress analysis: 99-percentile versus peak stress.

OBJECTIVE: Biomechanically, rupture of an Abdominal Aortic Aneurysm (AAA) occurs when the stress acting on the wall due to the blood pressure, exceeds the strength of the wall. Peak wall stress estimations, based on CT reconstruction, may be prone to observer variation. This study focuses on the robustness and reproducibility of AAA wall stress assessment and the relation with geometrical features of the AAA. METHODS: The AAAs of twenty patients were reconstructed by three operators. Both the peak and 99-percentile stress were used for intra- and inter-operator variability using the intraclass correlation coefficient (ICC). A regression analysis was performed to relate the stress parameters with the maximum diameter. Outliers were analyzed by their geometrical characteristics. RESULTS: The intra-operator ICC was 0.73-0.79 for the peak stress and 0.94 for the 99-percentile stress. The inter-operator ICC was 0.71 for the peak stress and 0.95 for the 99-percentile stress. A significant linear relation with the diameter was found only for the 99-percentile stress. CONCLUSIONS: The 99-percentile stress is more reproducible than peak wall stress. A significant relation between wall stress and diameter was found. Other geometrical features had no statistical relation with high stress.

Towards patient-specific risk assessment of abdominal aortic aneurysm.

Diagnosis of vascular disease and selection and planning of therapy are to a large extent based on the geometry of the diseased vessel. Treatment of a particular vascular disease is usually considered if the geometrical parameter that characterizes the severity of the disease, e.g. % vessel narrowing, exceeds a threshold. The thresholds that are used in clinical practice are based on epidemiological knowledge, which has been obtained by clinical studies including large numbers of patients. They may apply "on average", but they can be sub-optimal for individual patients. To realize more patient-specific treatment decision criteria, more detailed knowledge may be required about the vascular hemodynamics, i.e. the blood flow and pressure in the diseased vessel and the biomechanical reaction of the vessel wall to this flow and pressure. Over the last decade, a substantial number of publications have appeared on hemodynamic modeling. Some studies have provided first evidence that this modeling may indeed be used to support therapeutic decisions. The goal of the research reported in this paper is to go one step further, namely to investigate the feasibility of a patient-specific hemodynamic modeling methodology that is not only effective (improves therapeutic decisions), but that is also efficient (easy to use, fast, as much as possible automatic) and robust (insensitive to variation in the quality of the input data, same outcome for different users). A review is presented of our research performed during the last 5 years and the results that were achieved. This research focused on the risk assessment for one particular disease, namely abdominal aortic aneurysm, a life-threatening dilatation of the abdominal aorta.

A numerical model to predict abdominal aortic aneurysm expansion based on local wall stress and stiffness.

Aneurysms of the abdominal aorta enlarge until rupture occurs. We assume that this is the result of remodelling to restore wall stress. We developed a numerical model to predict aneurysm expansion based on this assumption. In addition, we obtained aneurysm geometry of 11 patients from computed tomography angiographic images to obtain patient specific calculations. The assumption of a wall stress related expansion indeed resulted in a series of local expansions, adjusting global geometry in an exponential fashion similar as in patients. Furthermore, it revealed that location of peak wall stress changed over time. The assumptions of this model are discussed in detail in this manuscript, and the implications are related to literature findings.

Patient-specific initial wall stress in abdominal aortic aneurysms with a backward incremental method.

Patient-specific wall stress simulations on abdominal aortic aneurysms may provide a better criterion for surgical intervention than the currently used maximum transverse diameter. In these simulations, it is common practice to compute the peak wall stress by applying the full systolic pressure directly on the aneurysm geometry as it appears in medical images. Since this approach does not account for the fact that the measured geometry is already experiencing a substantial load, it may lead to an incorrect systolic aneurysm shape. We have developed an approach to compute the wall stress on the true diastolic geometry at a given pressure with a backward incremental method. The method has been evaluated with a neo-Hookean material law for several simple test problems. The results show that the method can predict an unloaded configuration if the loaded geometry and the load applied are known. The effect of incorporating the initial diastolic stress has been assessed by using three patient-specific geometries acquired with cardiac triggered MR. The comparison shows that the commonly used approach leads to an unrealistically smooth systolic geometry and therefore provides an underestimation for the peak wall stress. Our backward incremental modelling approach overcomes these issues and provides a more plausible estimate for the systolic aneurysm volume and a significantly different estimate for the peak wall stress. When the approach is applied with a more complex material law which has been proposed specifically for abdominal aortic aneurysm similar effects are observed and the same conclusion can be drawn.

The EASI project--improving the effectiveness and quality of image-guided surgery.

In recent years, advances in computer technology and a significant increase in the accuracy of medical imaging have made it possible to develop systems that can assist the clinician in diagnosis, planning, and treatment. This paper deals with an area that is generally referred to as computer-assisted surgery, image-directed surgery, or image-guided surgery. We report the research, development, and clinical validation performed since January 1996 in the European Applications in Surgical Interventions (EASI) project, which is funded by the European Commission in their "4th Framework Telematics Applications for Health" program. The goal of this project is the improvement of the effectiveness and quality of image-guided neurosurgery of the brain and image-guided vascular surgery of abdominal aortic aneurysms, while at the same time reducing patient risks and overall cost. We have developed advanced prototype systems for preoperative surgical planning and intraoperative surgical navigation, and we have extensively clinically validated these systems. The prototype systems and the clinical validation results are described in this paper.

Data compression of x-ray cardio-angiographic image series.

Medical x-ray images are increasingly stored and transmitted in a digital format. To reduce the required storage space and transmission bandwidth, data compression can be applied. In this paper we describe a new method for data compression of cardio-angiographic x-ray image series. The method is based on so-called overlapped-transform coding. A comparison with the well-known block-based transform-coding methods JPEG and MPEG is presented. We found that overlapped-transform coding does not introduce any blocking artefacts, in contrast to block-based transform coding, which introduces clearly visible blocking artefacts at compression ratios above 8. Clinical evaluations of the new method have pointed out that the image quality obtained at a compression ratio of 12 is adequate for diagnostic applications.

Facilitated nuclear transport of histone H1 and other small nucleophilic proteins.

Upon microinjection into the cytoplasm, three small nonnuclear (extracellular or mitochondrial) proteins diffused into nuclei of chilled or energy-depleted cells. In contrast, the facilitated transport of two large nuclear localization signal (NLS)-containing proteins was reversibly arrested by chilling or energy depletion. Surprisingly, the transport of two small nucleophilic proteins, histone H1 and P(Lys)-cytochrome c (cytochrome c cross-linked with synthetic peptide NLSs), was also arrested by either chilling or energy depletion. In situ titration studies indicate that the transport arrest of H1 in chilled cells is mediated by a cytoplasmic receptor. Therefore, even though they are potentially able to diffuse into nuclei, histones and other small NLS-containing proteins are localized by a receptor-mediated process that precludes their diffusion through the nuclear pores.

Speechreading supplemented with auditorily presented speech parameters.

Results are reported from two experiments in which the benefit of supplementing speechreading with auditorily presented information about the speech signal was investigated. In experiment I, speechreading was supplemented with information about the prosody of the speech signal. For ten normal-hearing subjects with no experience in speechreading, the intelligibility score for sentences increased significantly when speechreading was supplemented with information about the overall amplitude of the speech signal, information about the fundamental frequency, or both. Binary information about voicing appeared not to be a significant supplement. In experiment II, the best-scoring supplements of experiment I were compared with two supplementary signals from our previous studies, i.e., information about the sound-pressure levels in two 1-oct filter bands centered at 500 and 3160 Hz, or information about the frequencies of the first and second formants from voiced speech segments. Sentence-intelligibility scores were measured for 24 normal-hearing subjects with no experience in speechreading, and for 12 normal-hearing experienced speechreaders. For the inexperienced speechreaders, the sound-pressure levels appeared to be the best supplement (87.1% correct syllables). For the experienced speechreaders, the formant-frequency information (88.6% correct), and the fundamental-frequency plus amplitude information (86.0% correct), were equally efficient supplements as the sound-pressure information (86.1% correct). Discrimination of phonemes (both consonants and vowels) was measured for the group of 24 inexperienced speechreaders. Percentage correct responses, confusion among phonemes, and the percentage of transmitted information about different types of manner and place of articulation and about the feature voicing are presented.

Speechreading supplemented with formant-frequency information from voiced speech.

The benefit of supplementing speechreading with information about the frequencies of the first and second formants from the voiced sections of the speech signal was studied by presenting short sentences to 18 normal-hearing listeners under the following three conditions: (a) speechreading combined with listening to the formant-frequency information, (b) speechreading only, and (c) formant-frequency information only. The formant frequencies were presented either as pure tones or as a complex speechlike signal, obtained by filtering a periodic pulse sequence of 250 Hz by a cascade of four second-order bandpass filters (with constant bandwidth); the center frequencies of two of these filters followed the frequencies of the first and second formants, whereas the frequencies of the others remained constant. The percentage of correctly identified syllables increased from 22.8 in the case of speechreading only to 82.0 in the case of speechreading while listening to the complex speechlike signal. Listening to the formant information only scored 33.2% correct. However, comparison with the best-scoring condition of our previous study [Breeuwer and Plomp, J. Acoust. Soc. Am. 76, 686-691 (1984)] indicates that information about the sound-pressure levels in two one-octave filter bands with center frequencies of 500 and 3160 Hz is a more effective supplement to speechreading than the formant-frequency information.

Speechreading supplemented with frequency-selective sound-pressure information.

The benefit of supplementing speechreading with frequency-selective sound-pressure information was studied by auditorily presenting this information to normal-hearing listeners. The sound-pressure levels in one or two frequency bands of the speech signal with center frequencies of 500, 1600, and 3160 Hz, respectively, and with 1- or 1/3-oct bandwidth were used to amplitude-modulate pure-tone carriers with frequencies equal to the center frequencies of the filter bands. Short sentences were presented to 18 normal-hearing listeners under the conditions of speechreading-only and speechreading combined with the sound-pressure information. The mean number of correctly perceived syllables increased from 22.8% for speechreading-only to 65.7% when sound-pressure information was supplied in a single 1-oct band at 500 Hz and to 86.7% with two 1-oct bands at 500 and 3160 Hz, respectively. The latter signal scored only 26.7% correct syllables without accompanying visual information.