Quantification of the methodological error in kinematic evaluation of the DRUJ using dynamic CT.

Distal radio-ulnar joint (DRUJ) motion analysis using dynamic CT is gaining popularity. Following scanning and segmentation, 3D bone models are registered to (4D-)CT target frames. Imaging errors like low signal-to-noise ratio (SNR), limited Z-coverage and motion artefacts influence registration, causing misinterpretation of joint motion. This necessitates quantification of the methodological error. A cadaver arm and dynamic phantom were subjected to multiple 4D-CT scans, while varying tube charge-time product and phantom angular velocity, to evaluate the effects of SNR and motion artefacts on registration accuracy and precision. 4D-CT Z-coverage is limited by the scanner. To quantify the effects of different Z-coverages on registration accuracy and precision, 4D-CT was simulated by acquiring multiple spiral 3D-CT scans of the cadaver arm. Z-coverage was varied by clipping the 3D bone models prior to registration. The radius position relative to the ulna was obtained from the segmentation image. Apparent relative displacement seen in the target images is caused by registration errors. Worst-case translations were 0.45, 0.08 and 1.1 mm for SNR-, Z-coverage- and motion-related errors respectively. Worst-case rotations were 0.41, 0.13 and 6.0 degrees. This study showed that quantification of the methodological error enables composition of accurate and precise DRUJ motion scanning protocols.

Comparison of postmortem whole-body contrast-enhanced microfocus computed tomography and high-field magnetic resonance imaging of human fetuses.

OBJECTIVE: Although fetal autopsy is generally recommended to confirm or refute the antemortem diagnosis, parental acceptance of the procedure has fallen over time, mainly due to its invasiveness. Contrast-enhanced microfocus CT (micro-CT) and high-field magnetic resonance imaging (HF-MRI, ≥ 3 Tesla) have both been suggested as non-invasive alternatives to conventional fetal autopsy for fetuses < 20 weeks of gestation. The aim of this study was to compare these two modalities in postmortem whole-body fetal imaging. METHODS: In this study, the imaging process and quality of micro-CT and HF-MRI were compared using both qualitative and quantitative assessments. For the qualitative evaluation, fetal anatomy experts scored 56 HF-MRI and 56 micro-CT images of four human fetuses aged 13-18 gestational weeks on two components: overall image quality and the ability to recognize and assess 21 anatomical structures. For the quantitative evaluation, participants segmented manually three organs with increasing complexity to assess interobserver variability. In addition, the signal-to-noise and contrast-to-noise ratios of five major organs were determined. RESULTS: Both imaging techniques were able to reach submillimeter voxel size. The highest resolution of micro-CT was 22 µm (isotropic), while the highest resolution of HF-MRI was 137 µm (isotropic). The qualitative image assessment form was sent to 45 fetal anatomy experts, of whom 36 (80%) responded. It was observed that micro-CT scored higher on all components of the qualitative assessment compared with HF-MRI. In addition, the quantitative assessment showed that micro-CT had lower interobserver variability and higher signal-to-noise and contrast-to-noise ratios. CONCLUSIONS: Our findings show that micro-CT outperforms HF-MRI in postmortem whole-body fetal imaging in terms of both quantitative and qualitative outcomes. Combined, these findings suggest that the ability to extract diagnostic information is greater when assessing micro-CT compared with HF-MRI images. We, therefore, believe that micro-CT is the preferred imaging modality as an alternative to conventional fetal autopsy for early gestation and is an indispensable tool in postmortem imaging services. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Reducing soft-tissue shrinkage artefacts caused by staining with Lugol's solution.

Diffusible iodine-based contrast-enhanced computed tomography (diceCT) is progressively used in clinical and morphological research to study developmental anatomy. Lugol's solution (Lugol) has gained interest as an effective contrast agent; however, usage is limited due to extensive soft-tissue shrinkage. The mechanism of Lugol-induced shrinkage and how to prevent it is largely unknown, hampering applications of Lugol in clinical or forensic cases where tissue shrinkage can lead to erroneous diagnostic conclusions. Shrinkage was suggested to be due to an osmotic imbalance between tissue and solution. Pilot experiments pointed to acidification of Lugol, but the relation of acidification and tissue shrinkage was not evaluated. In this study, we analyzed the relation between tissue shrinkage, osmolarity and acidification of the solution during staining. Changes in tissue volume were measured on 2D-segmented magnetic resonance and diceCT images using AMIRA software. Partial correlation and stepwise regression analysis showed that acidification of Lugol is the main cause of tissue shrinkage. To prevent acidification, we developed a buffered Lugol's solution (B-Lugol) and showed that stabilizing its pH almost completely prevented shrinkage without affecting staining. Changing from Lugol to B-Lugol is a major improvement for clinical and morphological research and only requires a minor adaptation of the staining protocol.

A 3D printed cast for minimally invasive transfer of distal radius osteotomy: a cadaver study.

PURPOSE: In corrective osteotomy of the distal radius, patient-specific 3D printed surgical guides or optical navigation systems are often used to navigate the surgical saw. The purpose of this cadaver study is to present and evaluate a novel cast-based guiding system to transfer the virtually planned corrective osteotomy of the distal radius. METHODS: We developed a cast-based guiding system composed of a cast featuring two drilling slots as well as an external cutting guide that was used to orient the surgical saw for osteotomy in the preoperatively planned position. The device was tested on five cadaver specimens with different body fat percentages. A repositioning experiment was performed to assess the precision of replacing an arm in the cast. Accuracy and precision of drilling and cutting using the proposed cast-based guiding system were evaluated using the same five cadaver arms. CT imaging was used to quantify the positioning errors in 3D. RESULTS: For normal-weight cadavers, the resulting total translation and rotation repositioning errors were ± 2 mm and ± 2°. Across the five performed surgeries, the median accuracy and Inter Quartile Ranges (IQR) of pre-operatively planned drilling trajectories were 4.3° (IQR = 2.4°) and 3.1 mm (IQR = 4.9 mm). Median rotational and translational errors in transferring the pre-operatively planned osteotomy plane were and 3.9° (IQR = 4.5°) and 2.6 mm (IQR = 4.2 mm), respectively. CONCLUSION: For normal weight arm specimens, navigation of corrective osteotomy via a cast-based guide resulted in transfer errors comparable to those using invasive surgical guides. The promising positioning capabilities justify further investigating whether the method could ultimately be used in a clinical setting, which could especially be of interest when used with less invasive osteosynthesis material.

High Spatiotemporal Resolution 4D Flow MRI of Intracranial Aneurysms at 7T in 10 Minutes.

BACKGROUND AND PURPOSE: Patients with intracranial aneurysms may benefit from 4D flow MR imaging because the derived wall shear stress is considered a useful marker for risk assessment and growth of aneurysms. However, long scan times limit the clinical implementation of 4D flow MR imaging. Therefore, this study aimed to investigate whether highly accelerated, high resolution, 4D flow MR imaging at 7T provides reliable quantitative blood flow values in intracranial arteries and aneurysms. MATERIALS AND METHODS: We used pseudospiral Cartesian undersampling with compressed sensing reconstruction to achieve high spatiotemporal resolution (0.5 mm isotropic, ∼30 ms) in a scan time of 10 minutes. We analyzed the repeatability of accelerated 4D flow scans and compared flow rates, stroke volume, and the pulsatility index with 2D flow and conventional 4D flow MR imaging in a flow phantom and 15 healthy subjects. Additionally, accelerated 4D flow MR imaging with high spatiotemporal resolution was acquired in 5 patients with aneurysms to derive wall shear stress. RESULTS: Flow-rate bias compared with 2D flow was lower for accelerated than for conventional 4D flow MR imaging (0.31 ± 0.13, P = .22, versus 0.79 ± 0.17 mL/s, P < .01). Pulsatility index bias gave similar results. Stroke volume bias showed no difference for accelerated as well as for conventional 4D flow compared to 2D flow MR imaging. Repeatability for accelerated 4D flow was similar to that of 2D flow MR imaging. Increased temporal resolution for wall shear stress measurements in 5 intracranial aneurysms did not show a consistent effect for the wall shear stress but did show an effect for the oscillatory shear index. CONCLUSIONS: Highly accelerated high spatiotemporal resolution 4D flow MR imaging at 7T in intracranial arteries and aneurysms provides repeatable and accurate quantitative flow values. Flow rate accuracy is significantly increased compared with conventional 4D flow scans.

Novel imaging techniques to study postmortem human fetal anatomy: a systematic review on microfocus-CT and ultra-high-field MRI.

BACKGROUND: MRI and CT have been extensively used to study fetal anatomy for research and diagnostic purposes, enabling minimally invasive autopsy and giving insight in human fetal development. Novel (contrast-enhanced) microfocus CT (micro-CT) and ultra-high-field (≥ 7.0 T) MRI (UHF-MRI) techniques now enable micron-level resolution that combats the disadvantages of low-field MRI and conventional CT. Thereby, they might be suitable to study fetal anatomy in high detail and, in time, contribute to the postmortem diagnosis of fetal conditions. OBJECTIVES: (1) To systematically examine the usability of micro-CT and UHF-MRI to study postmortem human fetal anatomy, and (2) to analyze factors that govern success at each step of the specimen preparation and imaging. METHOD: MEDLINE and EMBASE were systematically searched to identify publications on fetal imaging by micro-CT or UHF-MRI. Scanning protocols were summarized and best practices concerning specimen preparation and imaging were enumerated. RESULTS: Thirty-two publications reporting on micro-CT and UHF-MRI were included. The majority of the publications focused on imaging organs separately and seven publications focused on whole body imaging, demonstrating the possibility of visualization of small anatomical structures with a resolution well below 100 µm. When imaging soft tissues by micro-CT, the fetus should be stained by immersion in Lugol's staining solution. CONCLUSION: Micro-CT and UHF-MRI are both excellent imaging techniques to provide detailed images of gross anatomy of human fetuses. The present study offers an overview of the current best practices when using micro-CT and/or UHF-MRI to study fetal anatomy for clinical and research purposes. KEY POINTS: • Micro-CT and UHF-MRI can both be used to study postmortem human fetal anatomy for clinical and research purposes. • Micro-CT enables high-resolution imaging of fetal specimens in relatively short scanning time. However, tissue staining using a contrast solution is necessary to enable soft-tissue visualization. • UHF-MRI enables high-resolution imaging of fetal specimens, without the necessity of prior staining, but with the drawback of long scanning time.

Data-efficient deep learning of radiological image data for outcome prediction after endovascular treatment of patients with acute ischemic stroke.

Treatment selection is becoming increasingly more important in acute ischemic stroke patient care. Clinical variables and radiological image biomarkers (old age, pre-stroke mRS, NIHSS, occlusion location, ASPECTS, among others) have an important role in treatment selection and prognosis. Radiological biomarkers require expert annotation and are subject to inter-observer variability. Recently, Deep Learning has been introduced to reproduce these radiological image biomarkers. Instead of reproducing these biomarkers, in this work, we investigated Deep Learning techniques for building models to directly predict good reperfusion after endovascular treatment (EVT) and good functional outcome using CT angiography images. These models do not require image annotation and are fast to compute. We compare the Deep Learning models to Machine Learning models using traditional radiological image biomarkers. We explored Residual Neural Network (ResNet) architectures, adapted them with Structured Receptive Fields (RFNN) and auto-encoders (AE) for network weight initialization. We further included model visualization techniques to provide insight into the network's decision-making process. We applied the methods on the MR CLEAN Registry dataset with 1301 patients. The Deep Learning models outperformed the models using traditional radiological image biomarkers in three out of four cross-validation folds for functional outcome (average AUC of 0.71) and for all folds for reperfusion (average AUC of 0.65). Model visualization showed that the arteries were relevant features for functional outcome prediction. The best results were obtained for the ResNet models with RFNN. Auto-encoder initialization often improved the results. We concluded that, in our dataset, automated image analysis with Deep Learning methods outperforms radiological image biomarkers for stroke outcome prediction and has the potential to improve treatment selection.

Evaluation of compressed sensing MRI for accelerated bowel motility imaging.

BACKGROUND: To investigate the feasibility of compressed sensing and parallel imaging (CS-PI)-accelerated bowel motility magnetic resonance imaging (MRI) and to compare its image quality and diagnostic quality to conventional sensitivity encoding (SENSE) accelerated scans. METHODS: Bowel MRI was performed in six volunteers using a three-dimensional balanced fast field-echo sequence. Static scans were performed after the administration of a spasmolytic agent to prevent bowel motion artefacts. Fully sampled reference scans and multiple prospectively 3× to 7× undersampled CS-PI and SENSE scans were acquired. Additionally, fully sampled CS-PI and SENSE scans were retrospectively undersampled and reconstructed. Dynamic scans were performed using 5× to 7× accelerated scans in the presence of bowel motion. Retrospectively, undersampled scans were compared to fully sampled scans using structural similarity indices. All reconstructions were visually assessed for image quality and diagnostic quality by two radiologists. RESULTS: For static imaging, the performance of CS-PI was lower than that of fully sampled and SENSE scans: the diagnostic quality was assessed as adequate or good for 100% of fully sampled scans, 95% of SENSE, but only for 55% of CS-PI scans. For dynamic imaging, CS-PI image quality was scored similar to SENSE at high acceleration. Diagnostic quality of all scans was scored as adequate or good; 55% of CS-PI and 83% of SENSE scans were scored as good. CONCLUSION: Compared to SENSE, current implementation of CS-PI performed less or equally good in terms of image quality and diagnostic quality. CS-PI did not show advantages over SENSE for three-dimensional bowel motility imaging.

Myoglobin and troponin concentrations are increased in early stage deep tissue injury.

Pressure-induced deep tissue injury is a form of pressure ulcer which is difficult to detect and diagnose at an early stage, before the wound has severely progressed and becomes visible at the skin surface. At the present time, no such detection technique is available. To test the hypothesis that muscle damage biomarkers can be indicative of the development of deep tissue injury after sustained mechanical loading, an indentation test was performed for 2 h on the tibialis anterior muscle of rats. Myoglobin and troponin were analysed in blood plasma and urine over a period of 5 days. The damage as detected by the biomarkers was compared to damage as observed with T2 MRI to validate the response. We found that myoglobin and troponin levels in blood increased due to the damage. Myoglobin was also increased in urine. The amount of damage observed with MRI immediately after loading had a strong correlation with the maximal biomarker levels: troponin in blood rs = 0.94; myoglobin in blood rs = 0.75; and myoglobin in urine rs = 0.57. This study suggests that muscle damage markers measured in blood and urine could serve as early diagnosis for pressure induced deep tissue injury.

Implementation of a semiautomatic method to design patient-specific instruments for corrective osteotomy of the radius.

PURPOSE: 3D-printed patient-specific instruments (PSIs), such as surgical guides and implants, show great promise for accurate navigation in surgical correction of post-traumatic deformities of the distal radius. However, existing costs of computer-aided design and manufacturing process prevent everyday surgical use. In this paper, we propose an innovative semiautomatic methodology to streamline the PSIs design. METHODS: The new method was implemented as an extension of our existing 3D planning software. It facilitates the design of a regular and smooth implant and a companion guide starting from a user-selected surface on the affected bone. We evaluated the software by designing PSIs starting from preoperative virtual 3D plans of five patients previously treated at our institute for corrective osteotomy. We repeated the design for the same cases also with commercially available software, with and without dedicated customization. We measured design time and tracked user activity during the design process of implants, guides and subsequent modifications. RESULTS: All the designed shapes were considered valid. Median design times ([Formula: see text]) were reduced for implants (([Formula: see text]) = 2.2 min) and guides (([Formula: see text]) = 1.0 min) compared to the standard (([Formula: see text]) = 13 min and ([Formula: see text]) = 8 min) and the partially customized (([Formula: see text]) = 6.5 min and ([Formula: see text]) = 6.0 min) commercially available alternatives. Mouse and keyboard activities were reduced (median count of strokes and clicks during implant design (([Formula: see text]) = 53, and guide design (([Formula: see text]) = 27) compared to using standard software (([Formula: see text]) = 559 and ([Formula: see text]) = 380) and customized commercial software (([Formula: see text]) = 217 and ([Formula: see text]) = 180). CONCLUSION: Our software solution efficiently streamlines the design of PSIs for distal radius malunion. It represents a first step in making 3D-printed PSIs technology more accessible.

Biomechanical considerations in the design of patient-specific fixation plates for the distal radius.

Use of patient-specific fixation plates is promising in corrective osteotomy of the distal radius. So far, custom plates were mostly shaped to closely fit onto the bone surface and ensure accurate positioning of bone segments, however, without considering the biomechanical needs for bone healing. In this study, we investigated how custom plates can be optimized to stimulate callus formation under daily loading conditions. We calculated implant stress distributions, axial screw forces, and interfragmentary strains via finite element analysis (FEA) and compared these parameters for a corrective distal radius osteotomy model fixated by standard and custom plates. We then evaluated these parameters in a modified custom plate design with alternative screw configuration, plate size, and thickness on 5 radii models. Compared to initial design, in the modified custom plate, the maximum stress was reduced, especially under torsional load (- 31%). Under bending load, implants with 1.9-mm thickness induced an average strain (median = 2.14%, IQR = 0.2) in the recommended range (2-10%) to promote callus formation. Optimizing the plate shape, width, and thickness in order to keep the fixation stable while guaranteeing sufficient strain to enhance callus formation can be considered as a design criteria for future, less invasive, custom distal radius plates. Graphical abstract ᅟ.

Breast magnetic resonance elastography: a review of clinical work and future perspectives.

This review on magnetic resonance elastography (MRE) of the breast provides an overview of available literature and describes current developments in the field of breast MRE, including new transducer technology for data acquisition and multi-frequency-derived power-law behaviour of tissue. Moreover, we discuss the future potential of breast MRE, which goes beyond its original application as an additional tool in differentiating benign from malignant breast lesions. These areas of ongoing and future research include MRE for pre-operative tumour delineation, staging, monitoring and predicting response to treatment, as well as prediction of the metastatic potential of primary tumours.

Positioning error of custom 3D-printed surgical guides for the radius: influence of fitting location and guide design.

PURPOSE: Utilization of 3D-printed patient-specific surgical guides is a promising navigation approach for orthopedic surgery. However, navigation errors can arise if the guide is not correctly positioned at the planned bone location, compromising the surgical outcome. Quantitative measurements of guide positioning errors are rarely reported and have never been related to guide design and underlying bone anatomy. In this study, the positioning accuracy of a standard and an extended guide design with lateral extension is evaluated at different fitting locations (distal, mid-shaft and proximal) on the volar side of the radius. METHODS: Four operators placed the surgical guides on 3D-printed radius models obtained from the CT scans of six patients. For each radius model, every operator positioned two guide designs on the three fitting locations. The residual positioning error was quantified with a CT-based image analysis method in terms of the mean target registration error (mTRE), total translation error ([Formula: see text]) and total rotation error ([Formula: see text]) by comparing the actual guide position with the preoperatively planned position. Three generalized linear regression models were constructed to evaluate if the fitting location and the guide design affected mTRE, [Formula: see text] and [Formula: see text]. RESULTS: mTRE, [Formula: see text] and [Formula: see text] were significantly higher for mid-shaft guides ([Formula: see text]) compared to distal guides. The guide extension significantly improved the target registration and translational accuracy in all the volar radius locations ([Formula: see text]). However, in the mid-shaft region, the guide extension yielded an increased total rotational error ([Formula: see text]). CONCLUSION: Our study demonstrates that positioning accuracy depends on the fitting location and on the guide design. In distal and proximal radial regions, the accuracy of guides with lateral extension is higher than standard guides and is therefore recommended for future use.

Cardiac 4D phase-contrast CMR at 9.4 T using self-gated ultra-short echo time (UTE) imaging.

BACKGROUND: Time resolved 4D phase contrast (PC) cardiovascular magnetic resonance (CMR) in mice is challenging due to long scan times, small animal ECG-gating and the rapid blood flow and cardiac motion of small rodents. To overcome several of these technical challenges we implemented a retrospectively self-gated 4D PC radial ultra-short echo-time (UTE) acquisition scheme and assessed its performance in healthy mice by comparing the results with those obtained with an ECG-triggered 4D PC fast low angle shot (FLASH) sequence. METHODS: Cardiac 4D PC CMR images were acquired at 9.4 T in healthy mice using the proposed self-gated radial center-out UTE acquisition scheme (TE/TR of 0.5 ms/3.1 ms) and a standard Cartesian 4D PC imaging sequence (TE/TR of 2.1 ms/5.0 ms) with a four-point Hadamard flow encoding scheme. To validate the proposed UTE flow imaging technique, experiments on a flow phantom with variable pump rates were performed. RESULTS: The anatomical images and flow velocity maps of the proposed 4D PC UTE technique showed reduced artifacts and an improved SNR (left ventricular cavity (LV): 8.9 ± 2.5, myocardium (MC): 15.7 ± 1.9) compared to those obtained using a typical Cartesian FLASH sequence (LV: 5.6 ± 1.2, MC: 10.1 ± 1.4) that was used as a reference. With both sequences comparable flow velocities were obtained in the flow phantom as well as in the ascending aorta (UTE: 132.8 ± 18.3 cm/s, FLASH: 134.7 ± 13.4 cm/s) and pulmonary artery (UTE: 78.5 ± 15.4 cm/s, FLASH: 86.6 ± 6.2 cm/s) of the animals. Self-gated navigator signals derived from information of the oversampled k-space center were successfully extracted for all animals with a higher gating efficiency of time spent on acquiring gated data versus total measurement time (UTE: 61.8 ± 11.5%, FLASH: 48.5 ± 4.9%). CONCLUSIONS: The proposed self-gated 4D PC UTE sequence enables robust and accurate flow velocity mapping of the mouse heart in vivo at high magnetic fields. At the same time SNR, gating efficiency, flow artifacts and image quality all improved compared to the images obtained using the well-established, ECG-triggered, 4D PC FLASH sequence.

A comparative analysis of the collagen architecture in the carotid artery: second harmonic generation versus diffusion tensor imaging.

Collagen is the main load-bearing component of the artery. The 3D arrangement of the collagen fibers is crucial to understand the mechanical behavior of such tissues. We compared collagen fiber alignment obtained by second harmonic generation (SHG) microscopy with the alignment obtained by diffusion tensor imaging (DTI) throughout the wall of a porcine carotid artery to check the feasibility of using DTI as a fast and non-destructive method instead of SHG. The middle part of the artery was cut into two segments: one for DTI and one for the SHG measurements. The tissue for SHG measurements was cut into 30µm tangential sections. After scanning all sections, they were registered together and the fiber orientation was quantified by an in-house algorithm. The tissue for DTI measurement was embedded in type VII agarose and scanned with an MRI-scanner. Fiber tractography was performed on the DTI images. Both methods showed a layered structure of the wall. The fibers were mainly oriented circumferentially in the outer adventitia and media. DTI revealed the predominant layers of the arterial wall. This study showed the feasibility of using DTI for evaluating the collagen orientation in native artery as a fast and non-destructive method.

Evaluation of the female pelvic floor in pelvic organ prolapse using 3.0-Tesla diffusion tensor imaging and fibre tractography.

OBJECTIVES: To prospectively explore the clinical application of diffusion tensor imaging (DTI) and fibre tractography in evaluating the pelvic floor. METHODS: Ten patients with pelvic organ prolapse, ten with pelvic floor symptoms and ten asymptomatic women were included. A two-dimensional (2D) spin-echo (SE) echo-planar imaging (EPI) sequence of the pelvic floor was acquired. Offline fibre tractography and morphological analysis of pelvic magnetic resonance imaging (MRI) were performed. Inter-rater agreement for quality assessment of fibre tracking results was evaluated using weighted kappa (κ). From agreed tracking results, eigen values (λ1, λ2, λ3), mean diffusivity (MD) and fractional anisotropy (FA) were calculated. MD and FA values were compared using ANOVA. Inter-rater reliability of DTI parameters was interpreted using the intra-class correlation coefficient (ICC). RESULTS: Substantial inter-rater agreement was found (κ = 0.71 [95% CI 0.63-0.78]). Four anatomical structures were reliably identified. Substantial inter-rater agreement was found for MD and FA (ICC 0.60-0.91). No significant differences between groups were observed for anal sphincter, perineal body and puboperineal muscle. A significant difference in FA was found for internal obturator muscle between the prolapse group and the asymptomatic group (0.27 ± 0.05 vs 0.22 ± 0.03; P = 0.015). CONCLUSION: DTI with fibre tractography permits identification of part of the clinically relevant pelvic structures. Overall, no significant differences in DTI parameters were found between groups. KEY POINTS: Diffusion tensor MRI offers new insights into female pelvic floor problems. DTI allows 3D visualisation and quantification of female pelvic floor anatomy. DTI parameters from pelvic floor structures can be reliably determined. No significant differences in DTI parameters between groups with/without prolapse.

Efficacy of positive contrast imaging techniques for molecular MRI of tumor angiogenesis.

Superparamagnetic iron oxide particles (SPIOs) are promising contrast agents for molecular MRI. To improve the in vivo detection of iron-based contrast media, positive contrast imaging techniques have been developed. Here, the efficacy of two positive contrast techniques, white marker and susceptibility gradient mapping (SGM), were evaluated for molecular MRI of tumor angiogenesis and compared with conventional negative contrast gradient echo (GE) imaging. In vitro, cylindrical phantoms containing varying iron oxide concentrations were used to measure the response of positive contrast techniques. In vivo, tumor bearing mice were used as a model for tumor angiogenesis. Mice were injected with unlabeled SPIOs (n = 5) or SPIOs labeled with cyclic NGR peptide (cNGR) (n = 5), which homes specifically to angiogenic microvessels. Pre- and post-contrast GE and white marker images were acquired. Subsequently, SGM images and R(2)(*) maps were calculated. For image analysis, the contrast-to-noise ratio (CNR) and the percentage of enhanced voxels (EVs) in the tumor rim and core were calculated. In vitro, the linear increases in MRI signal response for increasing iron oxide concentration were much stronger for SGM than white marker. In vivo, the CNR of GE, white marker and SGM imaging was 5.7, 1.2 and 6.2, respectively, with equal acquisition times. Significant differences in the percentage of EVs between the tumor rim and core were found using R(2)(*) mapping, GE and SGM (p < 0.05). The two contrast agents had significantly different percentages of EVs by R(2)(*) mapping and SGM in the rim (p < 0.001). The in vivo efficacy of white marker and SGM was evaluated for molecular MRI relative to GE imaging and R(2)(*) mapping. Only SGM, and not white marker, can be used to transfer the negative contrast from targeted SPIOs in a positive contrast signal without loss of CNR.

The effects of deformation, ischemia, and reperfusion on the development of muscle damage during prolonged loading.

Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. In the present study, the contributions of deformation, ischemia, and reperfusion to skeletal muscle damage development were examined in a rat model during a 6-h period. Magnetic resonance imaging (MRI) was used to study perfusion (contrast-enhanced MRI) and tissue integrity (T2-weighted MRI). The levels of tissue deformation were estimated using finite element models. Complete ischemia caused a gradual homogeneous increase in T2 (∼20% during the 6-h period). The effect of reperfusion on T2 was highly variable, depending on the anatomical location. In experiments involving deformation, inevitably associated with partial ischemia, a variable T2 increase (17-66% during the 6-h period) was observed reflecting the significant variation in deformation (with two-dimensional strain energies of 0.60-1.51 J/mm) and ischemia (50.8-99.8% of the leg) between experiments. These results imply that deformation, ischemia, and reperfusion all contribute to the damage process during prolonged loading, although their importance varies with time. The critical deformation threshold and period of ischemia that cause muscle damage will certainly vary between individuals. These variations are related to intrinsic factors, such as pathological state, which partly explain the individual susceptibility to the development of DTI and highlight the need for regular assessments of individual subjects.

Ischemia-reperfusion injury in rat skeletal muscle assessed with T2-weighted and dynamic contrast-enhanced MRI.

Pressure ulcers are localized areas of soft tissue breakdown due to mechanical loading. Susceptible individuals are subjected to pressure relief strategies to prevent long loading periods. Therefore, ischemia-reperfusion injury may play an important role in the etiology of pressure ulcers. To investigate the inter-relation between postischemic perfusion and changes in skeletal muscle integrity, the hindlimbs of Brown Norway rats were subjected to 4-h ischemia followed by 2-h reperfusion. Dynamic contrast-enhanced MRI was used to examine perfusion, and changes in skeletal muscle integrity were monitored with T2-weighted MRI. The dynamic contrast-enhanced MRI data showed a heterogeneous postischemic profile in the hindlimb, consisting of areas with increased contrast enhancement (14-76% of the hindlimb) and regions with no-reflow (5-77%). For T2, a gradual increase in the complete leg was observed during the 4-h ischemic period (from 34 to 41 msec). During the reperfusion phase, a heterogeneous distribution of T2 was observed. Areas with increased contrast enhancement were associated with a decrease in T2 (to 38 msec) toward preischemic levels, whereas no-reflow areas exhibited a further increase in T2 (to 42 msec). These results show that reperfusion after prolonged ischemia may not be complete, thereby continuing the ischemic condition and aggravating tissue damage.