Dapagliflozin Reduces Systemic Inflammation in Patients with Type 2 Diabetes Without Known Heart Failure.

Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis. Research and Design Methods: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); cardiac tissue inflammation was assessed by T2 mapping. Results: Between the baseline and 12-month time point, plasma IL-1B was reduced (-1.8 pg/mL, P=0.003) while ketones were increased (0.26 mM, P=0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (-158.9 pmole/min/106cells, P=0.0497 vs -45.2 pmole/min/106cells, P=0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. ECV and T2 relaxation time did not change in both study groups. Conclusion: This study demonstrates that 12 months of dapagliflozin reduces IL-1B mediated systemic inflammation but affect cardiac fibrosis in T2D. Clinical Trialgov Registration: NCT03782259.

Subject-specific material properties of the heel pad: An inverse finite element analysis.

Individuals with diabetes are at a higher risk of developing foot ulcers. To better understand internal soft tissue loading and potential treatment options, subject-specific finite element (FE) foot models have been used. However, existing models typically lack subject-specific soft tissue material properties and only utilize subject-specific anatomy. Therefore, this study determined subject-specific hindfoot soft tissue material properties from one non-diabetic and one diabetic subject using inverse FE analysis. Each subject underwent cyclic MRI experiments to simulate physiological gait and to obtain compressive force and three-dimensional soft tissue imaging data at 16 phases along the loading-unloading cycles. The FE models consisted of rigid bones and nearly-incompressible first-order Ogden hyperelastic skin, fat, and muscle (resulting in six independent material parameters). Then, calcaneus and loading platen kinematics were computed from imaging data and prescribed to the FE model. Two analyses were performed for each subject. First, the skin, fat, and muscle layers were lumped into a single generic soft tissue material and optimized to the platen force. Second, the skin, fat, and muscle material properties were individually determined by simultaneously optimizing for platen force, muscle vertical displacement, and skin mediolateral bulging. Our results indicated that compared to the individual without diabetes, the individual with diabetes had stiffer generic soft tissue behavior at high strain and that the only substantially stiffer multi-material layer was fat tissue. Thus, we suggest that this protocol serves as a guideline for exploring differences in non-diabetic and diabetic soft tissue material properties in a larger population.

Atherosclerotic carotid plaque characteristics vary with time from ischemic event: A multicenter, prospective magnetic resonance vessel wall imaging registry study.

Recent studies report that the rate of recurrent stroke is highest in the stages immediately following cerebral infarction and decreases over time in patients with atherosclerotic carotid stenosis. The purpose of this study was to identify temporal differences in early stage carotid plaque components from acute cerebrovascular ischemic events using carotid MRI. Carotid plaque images were obtained on 3 T MRI from 128 patients enrolled in MR-CAS. Among the 128 subjects, 53 were symptomatic and 75 asymptomatic. The symptomatic patients were classified into three groups based on interval from onset of symptoms to the date of the carotid MRI (Group <14 days; 15-30 days; and > 30 days). The volume of each plaque component was identified and quantified from MR images. The presence of juxtaluminal loose matrix/inflammation (LM/I) was identified as a possible indicator of inflammation on the luminal side. Plaque components were compared between groups using the Wilcoxon rank-sum or the Chi-square test. Patient characteristics and carotid plaque morphology were similar among all four groups. The median volume of LM/I in Group >30 days was significantly lower than in other groups (0 mm3 vs 12.3 mm3 and 18.1 mm3; p = 0.003). In addition, the prevalence of juxtaluminal LM/I decreased over time (ptrend = 0.002). There were no statistically significant differences in other plaque components between the symptomatic groups. The volume of LM/I was significantly smaller in Group >30 days and prevalence of juxtaluminal LM/I in the atherosclerotic carotid plaque was high in the early stages after events. This suggests that carotid plaques undergo rapid evolution after an acute cerebrovascular ischemic event.

Alterations in cerebral distal vascular features and effect on cognition in a high cardiovascular risk population: A prospective longitudinal study.

BACKGROUND: Alterations in cerebral vasculature are instrumental in affecting cognition. Current studies mainly focus on proximal large arteries and small vessels, while disregarding morphology and blood flow of the arteries between them (medium-to-large arteries). METHODS: In this prospective study, two types of non-contrast enhanced magnetic resonance angiography (NCE-MRA) techniques, simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) and 3D Time-of-flight (TOF), were used to measure vascular morphologic features in medium-to-large intracranial arteries. Grey matter (GM) tissue level perfusion was assessed with arterial spin labeling (ASL) MRI. Twenty-seven subjects at high cardiovascular risk underwent baseline and 12-month follow-up MRI to compare the relationship between morphological features measured by NCE MRA, GM CBF by ASL MRI, and cognitive function measured by the Montreal Cognitive Assessment (MoCA). RESULTS: Changes in both global medium-to-large arteries and posterior cerebral (PCA) distal artery length and branch numbers, measured on SNAP MRA, were significantly associated with alterations in MoCA scores (P < 0.01), after adjusting for clinical confounding factors, total brain volume, and total white matter lesion (WML) volume. There were no associations between MoCA scores and vascular features on TOF MRA or ASL GM CBF. CONCLUSIONS: Alterations in vascular features of distal medium-to-large arteries may be more sensitive for detecting potential changes in cognition than cerebral blood flow alterations at the parenchymal level captured by perfusion ASL. Hemodynamic information from distal medium-to-large arteries provides an additional tool to advance understanding of the vascular contributions to cognitive function.

Associations of intracranial artery length and branch number on non-contrast enhanced MRA with cognitive impairment in individuals with carotid atherosclerosis.

Developing novel risk markers for vascular contributions to cognitive impairment and dementia is important. This study aimed to extract total length, branch number and average tortuosity of intracranial distal arteries (A2, M2, P2 and more distal) from non-contrast enhanced magnetic resonance angiography (NCE-MRA) images, and explore their associations with global cognition. In 29 subjects (aged 40-90 years) with carotid atherosclerotic disease, the 3 intracranial vascular features on two NCE-MRA techniques (i.e. time of flight, TOF and simultaneous non-contrast angiography and intraplaque hemorrhage, SNAP) were extracted using a custom-developed software named iCafe. Arterial spin labeling (ASL) and phase contrast (PC) cerebral blood flow (CBF) were measured as references. Linear regression was performed to study their associations with global cognition, measured with the Montreal Cognitive Assessment (MoCA). Intracranial artery length and number of branches on NCE-MRA, ASL CBF and PC CBF were found to be positively associated with MoCA scores (P < 0.01). The associations remained significant for artery length and number of branches on NCE-MRA after adjusting for clinical covariates and white matter hyperintensity volume. Further adjustment of confounding factors of ASL CBF or PC CBF did not abolish the significant association for artery length and number of branches on TOF. Our findings suggest that intracranial vascular features, including artery length and number of branches, on NCE-MRA may be useful markers of cerebrovascular health and provide added information over conventional brain blood flow measurements in individuals with cognitive impairment.

Detection of Advanced Lesions of Atherosclerosis in Carotid Arteries Using 3-Dimensional Motion-Sensitized Driven-Equilibrium Prepared Rapid Gradient Echo (3D-MERGE) Magnetic Resonance Imaging as a Screening Tool.

BACKGROUND AND PURPOSE: Two-dimensional high-resolution multicontrast magnetic resonance imaging (2D-MC MRI) is currently the most reliable and reproducible noninvasive carotid vessel wall imaging technique. However, the long scan time required for 2D-MC MRI restricts its practical clinical application. Alternatively, 3-dimensional motion-sensitized driven-equilibrium prepared rapid gradient echo (3D-MERGE) vessel wall MRI can provide high isotropic resolution with extensive coverage in two minutes. In this study, we sought to prove that 3D-MERGE alone can serve as a screening tool to identify advanced carotid lesions. METHODS: Two hundred twenty-seven subjects suspected of recent ischemic stroke or transient ischemic attack were imaged using 2D-MC MRI with an imaging time of 30 minutes, then with 3D-MERGE with an imaging time of 2 minutes, on 3T-MRI scanners. Two experienced reviewers interpreted plaque components using 2D-MC MRI as the reference standard and categorized plaques using a modified American Heart Association lesion classification for MRI. Plaques of American Heart Association type IV and above were classified as advanced. Arteries of American Heart Association types I to II and III were categorized as normal or with early lesions, respectively. One radiologist independently reviewed only 3D-MERGE and labeled the plaques as advanced if they had a wall thickness of >2 mm with high or low signal intensity compared with the adjacent sternocleidomastoid muscle. Sensitivity, specificity, and accuracy for 3D-MERGE were calculated. RESULTS: Four hundred forty-nine arteries from 227 participants (mean age 61.2 years old, 64% male) were included in the analysis. Sensitivity, specificity, and accuracy for identification of advanced lesions on 3D-MERGE were 95.0% (95% CI, 91.8-97.2), 86.9% (95% CI, 81.4-92.0), 93.8% (95% CI, 91.1-95.8), respectively. CONCLUSIONS: 3D-MERGE can accurately identify advanced carotid atherosclerotic plaques in patients suspected of stroke or transient ischemic attack. It has a more extensive coverage and higher sensitivity and specificity for advanced plaque detection with a much shorter acquisition time than 2D-MC MRI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02017756.

Quantitative Assessment of the Intracranial Vasculature of Infants and Adults Using iCafe (Intracranial Artery Feature Extraction).

Comprehensive quantification of intracranial artery features may help to assess and understand regional variations of blood supply during early brain development and aging. We analyzed vasculature features of 27 healthy infants during natural sleep, 13 infants at 7-months (7.3 ± 1.0 month), and 14 infants at 12-months (11.7 ± 0.4 month), and 13 older healthy, awake adults (62.8 ± 8.7 years) to investigate age-related vascular differences as a preliminary study of vascular changes associated with brain development. 3D time-of-flight (TOF) magnetic resonance angiography (MRA) acquisitions were processed in iCafe, a technique to quantify arterial features (http://icafe.clatfd.cn), to characterize intracranial vasculature. Overall, adult subjects were found to have increased ACA length, tortuosity, and vasculature density compared to both 7-month-old and 12-month-old infants, as well as MCA length compared to 7-month-old infants. No brain laterality differences were observed for any vascular measures in either infant or adult age groups. Reduced skull and brain sharpness, indicative of increased head motion and brain/vascular pulsation, respectively, were observed in infants but not correlated with length, tortuosity, or vasculature density measures. Quantitative analysis of TOF MRA using iCafe may provide an objective approach for systematic study of infant brain vascular development and for clinical assessment of adult and pediatric brain vascular diseases.

Domain adaptive and fully automated carotid artery atherosclerotic lesion detection using an artificial intelligence approach (LATTE) on 3D MRI.

PURPOSE: To develop and evaluate a domain adaptive and fully automated review workflow (lesion assessment through tracklet evaluation, LATTE) for assessment of atherosclerotic disease in 3D carotid MR vessel wall imaging (MR VWI). METHODS: VWI of 279 subjects with carotid atherosclerosis were used to develop LATTE, mainly convolutional neural network (CNN)-based domain adaptive lesion classification after image quality assessment and artery of interest localization. Heterogeneity in test sets from various sites usually causes inferior CNN performance. With our novel unsupervised domain adaptation (DA), LATTE was designed to accurately classify arteries into normal arteries and early and advanced lesions without additional annotations on new datasets. VWI of 271 subjects from four datasets (eight sites) with slightly different imaging parameters/signal patterns were collected to assess the effectiveness of DA of LATTE using the area under the receiver operating characteristic curve (AUC) on all lesions and advanced lesions before and after DA. RESULTS: LATTE had good performance with advanced/all lesion classification, with the AUC of >0.88/0.83, significant improvements from >0.82/0.80 if without DA. CONCLUSIONS: LATTE can locate target arteries and distinguish carotid atherosclerotic lesions with consistently improved performance with DA on new datasets. It may be useful for carotid atherosclerosis detection and assessment on various clinical sites.

Vessel length on SNAP MRA and TOF MRA is a potential imaging biomarker for brain blood flow.

PURPOSE: To explore feasibility of using the vessel length on time-of-flight (TOF) or simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) MRA as an imaging biomarker for brain blood flow, by using arterial spin labeling (ASL) perfusion imaging and 3D phase contrast (PC) quantitative flow imaging as references. METHODS: In a population of thirty subjects with carotid atherosclerotic disease, the visible intracranial arteries on TOF and SNAP were semi-automatically traced and the total length of the distal segments was calculated with a dedicated software named iCafe. ASL blood flow was calculated automatically using the recommended hemodynamic model. PC blood flow was obtained by generating cross-sectional arterial images and semi-automatically drawing the lumen contours. Pearson correlation coefficients were used to assess the associations between the different whole-brain or hemispheric blood flow measurements. RESULTS: Under the imaging protocol used in this study, TOF vessel length was larger than SNAP vessel length (P < 0.001). Both whole-brain TOF and SNAP vessel length showed a correlation with whole brain ASL and 3D PC blood flow measurements, and the correlation coefficients were higher for SNAP vessel length (TOF vs ASL: R = 0.554, P = 0.002; SNAP vs ASL: R = 0.711, P < 0.001; TOF vs 3D PC: R = 0.358, P = 0.052; SNAP vs 3D PC: R = 0.425, P = 0.019). Similar correlation results were observed for the hemispheric measurements. Hemispheric asymmetry index of SNAP vessel length also showed a significant correlation with hemispheric asymmetry index of ASL cerebral blood flow (R = 0.770, P < 0.001). CONCLUSION: The results suggest that length of the visible intracranial arteries on TOF or SNAP MRA can serve as a potential imaging marker for brain blood flow.

Neural network enhanced 3D turbo spin echo for MR intracranial vessel wall imaging.

PURPOSE: To improve the signal-to-noise ratio (SNR) and image sharpness for whole brain isotropic 0.5 mm three-dimensional (3D) T1 weighted (T1w) turbo spin echo (TSE) intracranial vessel wall imaging (IVWI) at 3 T. METHODS: The variable flip angle (VFA) method enables useful optimization across scan efficiency, SNR and relaxation induced point spread function (PSF) for TSE imaging. A convolutional neural network (CNN) was developed to retrospectively enhance the acquired TSE image with PSF blurring. The previously developed VFA method to increase SNR at the expense of blur can be combined with the presented PSF correction to yield long echo train length (ETL) scan while the acquired image remains high SNR and sharp. The overall approach can enable an optimized solution for accelerated whole brain high-resolution 3D T1w TSE IVWI. Its performance was evaluated on healthy volunteers and patients. RESULTS: The PSF blurred image acquired by a long ETL scan can be enhanced by CNN to restore similar sharpness as a short ETL scan, which outperforms the traditional linear PSF enhancement approach. For accelerated whole brain IVWI on volunteers, the optimized isotropic 0.5 mm 3D T1w TSE sequence with CNN based PSF enhancement provides sufficient flow suppression and improved image quality. Preliminary results on patients further demonstrated its improved delineation for intracranial vessel wall and plaque morphology. CONCLUSION: The CNN enhanced VFA TSE imaging enables an overall image quality improvement for high-resolution 3D T1w IVWI, and may provide a better tradeoff across scan efficiency, SNR and PSF for 3D TSE acquisitions.

A novel sequence for simultaneous measurement of whole-brain static and dynamic MRA, intracranial vessel wall image, and T1 -weighted structural brain MRI.

PURPOSE: To propose a highly time-efficient imaging technique named improved simultaneous noncontrast angiography and intraplaque hemorrhage (iSNAP) for simultaneous assessment of lumen, vessel wall, and blood flow in intracranial arteries. METHODS: iSNAP consists of pulsed arterial spin labeling preparations and 3D golden angle radial acquisition. Images were reconstructed by k-space weighted image contrast (KWIC) method with optimized data-sharing strategies. Dynamic MRA for blood flow assessment was obtained from iSNAP by reconstruction at multiple inversion times and image subtraction, static MRA by both image subtraction approach and phase-sensitive inversion recovery technique, and vessel wall images by both reconstruction at zero-crossing time-point of blood and phase-sensitive inversion recovery. A T1 -weighted brain MRI was also reconstructed from iSNAP. Preliminary comparison of iSNAP against the dedicated dynamic MRA sequence 4D-TRANCE, MRA/vessel wall imaging sequence SNAP, and vessel wall imaging sequence T1 -weighted VISTA was performed in healthy volunteers and patients. RESULTS: iSNAP has whole-brain coverage and takes ~6.5 min. The dedicated reconstruction strategies are feasible for each iSNAP image contrast and beneficial for image SNR. iSNAP-dynamic MRA yields similar dynamic flow information as 4D-TRANCE and allows more flexible temporal resolution. The 2 types of iSNAP static MRA images complement each other in characterizing both proximal large arteries and distal small arteries. Depiction of vessel wall lesions in iSNAP vessel wall images is better than SNAP and may be similar to T1 -weighted VISTA, although the images are slightly blurred. CONCLUSION: iSNAP provides a time-efficient evaluation of intracranial arteries and may have great potential for comprehensive assessment of intracranial vascular conditions using a single sequence.

Characterization of Carotid Atherosclerotic Plaques Using 3-Dimensional MERGE Magnetic Resonance Imaging and Correlation With Stroke Risk Factors.

Background and Purpose- High-resolution magnetic resonance imaging is capable of characterizing carotid atherosclerotic plaque morphology and composition. Most reported carotid plaque imaging techniques are 2-dimensional (2D) based with limited longitudinal coverage of ≈30 mm, which may be insufficient for complete visualization of extracranial carotid atheroma. A 3D black-blood imaging technique, motion-sensitized driven equilibrium prepared rapid gradient echo technique (3D-MERGE) can provide larger coverage. We sought to use 3D-MERGE to investigate carotid atherosclerosis plaque distribution and to analyze their correlation with clinical information and stroke risk factors. Methods- From 5 hospitals in China, 97 subjects suspected of recent stroke or transient ischemic attack were imaged with 3D-MERGE within 2 weeks of symptoms using 3T magnetic resonance imaging. Images were analyzed by 2 reviewers. Plaque length was calculated and categorized as plaques within, partially outside, or completely outside of typical 2D magnetic resonance imaging coverage. Associations between plaque features and clinical information, stroke risk factors were assessed. Results- Ninety-seven subjects with 194 carotid arteries (70 men and 27 women, mean age 60 years) were analyzed. Of the 136 plaques identified, 68 (50%) were within, 46 (33.8%) were partially outside, and 22 (16.2%) were completely outside of 2D magnetic resonance imaging coverage. Total plaque length was significantly positively associated with male sex (P<0.001), hypertension (P=0.011), and history of smoking (P<0.001). Hypertensive subjects were more likely to have at least one plaque completely outside the 2D magnetic resonance imaging coverage than nonhypertensive subjects (P=0.007). Conclusions- The 3D-MERGE allows for the identification of substantially more carotid plaques than 2D black-blood techniques. The extent and distribution of plaque, identified by the larger coverage afforded by 3D-MERGE, were found to correlate significantly with male sex and risk factors that are common among patients with stroke, including hypertension and history of cigarette smoking.

Improved carotid lumen delineation on non-contrast MR angiography using SNAP (Simultaneous Non-Contrast Angiography and Intraplaque Hemorrhage) imaging.

PURPOSE: Simultaneous Non-Contrast Angiography and Intraplaque Hemorrhage (SNAP) was developed for improved imaging of intraplaque hemorrhage (IPH). Its signal polarity also allows for non-contrast time-of-flight MR angiography (TOF). This study sought to compare SNAP and TOF in delineating carotid lumen using contrast-enhanced MRA (CE-MRA) as the reference standard. MATERIALS AND METHODS: Two hundred and eighty-nine matched slices from 15 arteries among 11 subjects (9 males and 2 females, mean age of 72.1 ±â€¯8.6 years) with luminal stenosis on CE-MRA were studied. Cross-sectional slices centered around the carotid bifurcation were matched between the three MRA techniques (SNAP, TOF, and CE-MRA) and classified as slices with or without plaque (focal wall thickness ≥ 1.5 mm) by additional black-blood vessel wall MRI. Lumen area was measured using a Sobel gradient map for TOF and CE-MRA (magnitude images) and a polarity map for SNAP. Agreement between techniques for measuring lumen area and percent stenosis was evaluated using intraclass correlation coefficient (ICC) and paired t-test. RESULTS: Among the 289 matched slices, SNAP showed a higher agreement with CE-MRA than TOF for measuring lumen area (ICC: 0.93 vs. 0.83; p = 0.03). Agreement with CE-MRA was high for both SNAP and TOF in slices without plaque (ICC: 0.91 vs. 0.89; p > 0.05) but favored SNAP over TOF in slices with plaque (ICC: 0.93 vs. 0.80; p = 0.02). CONCLUSION: SNAP, assisted by signal polarity information, demonstrated a higher agreement with CE-MRA in delineating carotid lumen compared to TOF, particularly in slices with plaque where flow conditions may be more complex.

A preliminary study of patient-specific mechanical properties of diabetic and healthy plantar soft tissue from gated magnetic resonance imaging.

Foot loading rate, load magnitude, and the presence of diseases such as diabetes can all affect the mechanical properties of the plantar soft tissues of the human foot. The hydraulic plantar soft tissue reducer instrument was designed to gain insight into which variables are the most significant in determining these properties. It was used with gated magnetic resonance imaging to capture three-dimensional images of feet under dynamic loading conditions. Custom electronics controlled by LabVIEW software simultaneously recorded system pressure, which was then translated to applied force values based on calibration curves. Data were collected for two subjects, one without diabetes (Subject A) and one with diabetes (Subject B). For a 0.2-Hz loading rate, and strains 0.16, 0.18, 0.20, and 0.22, Subject A's average tangential heel pad stiffness was 10 N/mm and Subject B's was 24 N/mm. Maximum test loads were approximately 200 N. Loading rate and load magnitude limitations (both were lower than physiologic values) will continue to be addressed in the next version of the instrument. However, the current hydraulic plantar soft tissue reducer did produce a data set for healthy versus diabetic tissue stiffness that agrees with previous trends. These data are also being used to improve finite element analysis models of the foot as part of a related project.

The design and validation of a magnetic resonance imaging-compatible device for obtaining mechanical properties of plantar soft tissue via gated acquisition.

Changes in the mechanical properties of the plantar soft tissue in people with diabetes may contribute to the formation of plantar ulcers. Such ulcers have been shown to be in the causal pathway for lower extremity amputation. The hydraulic plantar soft tissue reducer (HyPSTER) was designed to measure in vivo, rate-dependent plantar soft tissue compressive force and three-dimensional deformations to help understand, predict, and prevent ulcer formation. These patient-specific values can then be used in an inverse finite element analysis to determine tissue moduli, and subsequently used in a foot model to show regions of high stress under a wide variety of loading conditions. The HyPSTER uses an actuator to drive a magnetic resonance imaging-compatible hydraulic loading platform. Pressure and actuator position were synchronized with gated magnetic resonance imaging acquisition. Achievable loading rates were slower than those found in normal walking because of a water-hammer effect (pressure wave ringing) in the hydraulic system when the actuator direction was changed rapidly. The subsequent verification tests were, therefore, performed at 0.2 Hz. The unloaded displacement accuracy of the system was within 0.31%. Compliance, presumably in the system's plastic components, caused a displacement loss of 5.7 mm during a 20-mm actuator test at 1354 N. This was accounted for with a target to actual calibration curve. The positional accuracy of the HyPSTER during loaded displacement verification tests from 3 to 9 mm against a silicone backstop was 95.9% with a precision of 98.7%. The HyPSTER generated minimal artifact in the magnetic resonance imaging scanner. Careful analysis of the synchronization of the HyPSTER and the magnetic resonance imaging scanner was performed. With some limitations, the HyPSTER provided key functionality in measuring dynamic, patient-specific plantar soft tissue mechanical properties.

Changes in measured size of atherosclerotic plaque calcifications in dual-energy CT of ex vivo carotid endarterectomy specimens: effect of monochromatic keV image reconstructions.

OBJECTIVE: The aim of this study was to compare the size of the calcifications measured on the different keV images to a histological standard. METHODS: Five ex vivo carotid endarterectomy (CEA) specimens were imaged with a dual-energy CT. CT images were reconstructed at different monochromatic spectral energies (40, 60, 77, 80, 100, 120, 140 keV). Cross-sectional area of the plaque calcifications present on each CT image was measured. The histological calcium areas on each corresponding CEA specimen were traced manually on digitised images of Toluidine Blue/Basic Fuchsin stained plastic sections. The CT images and corresponding histology sections were matched. The CT-derived calcium areas on each keV image were compared to the calcified area measurements by histology. RESULTS: A total of 107 histology sections were matched to corresponding CT images. The average calcified area per section by histology was 7.6 ± 7 mm(2) (range 0-26.4 mm(2)). There was no significant difference between the calcified areas measured by histology and those measured on CT-virtual monochromatic spectral (VMS) reconstructed images at 77 keV (P = 0.08), 80 keV (P = 0.20) and 100 keV (P = 0.14). CONCLUSIONS: Calcium area measured on the 80 keV image set was most comparable to the amount of calcium measured by histology.

Quantitative evaluation of high intensity signal on MIP images of carotid atherosclerotic plaques from routine TOF-MRA reveals elevated volumes of intraplaque hemorrhage and lipid rich necrotic core.

BACKGROUND: Carotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR. METHODS: Seventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR. RESULTS: For detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 - 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 - 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm(3) vs. 53.4 ± 56.3 mm(3), p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm(3) vs. 111.3 ± 122.7 mm(3), p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001). CONCLUSION: MIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.

A targeted high-efficiency angiogenesis strategy as therapy for myocardial infarction.

AIMS: The aim of this study was to prove that an intramyocardial injection of a mixture of low-dose human growth factor (HGF) plasmid and microbubbles (MB) in combination with insonation was an effective therapy for myocardial infarction. MAIN METHODS: Twenty dogs with myocardial infarction were divided into 4 groups: (1) HGF, MB and ultrasound (HGF-US/MB), (2) HGF and US (HGF-US), (3) HGF alone and (4) surgery alone (control). In the HGF-US/MB group, HGF plasmid DNA (500 µg) mixed with 0.5 ml of MB solution was injected 5 min after coronary occlusion followed by insonation. With the exception of the control group, the other dogs were divided into two groups, one treated with the HGF gene and insonation and the other with the HGF gene only. KEY FINDINGS: Compared to the HGF group, infarct size decreased from 32%±7% (control) to 23%±5% in the HGF-US/MB group 28 d later (P<0.05). Capillary density increased from 21.7±4.2/mm(2) (control) to 114.3±28.9/mm(2) in the HGF-US/MB group (P<0.01). Compared to the HGF group, there was a 14% decrease in the ratio of left ventricle weight/body weight and a 25% decrease in hydroxyproline content. We also observed a 29% and 20% decrease in collagen volume fraction of type I and type III collagen, respectively in the HGF-US/MB group. SIGNIFICANCE: Intramyocardial injection of HGF and MB in combination with insonation enhances neovascularization and reduces ventricular remodeling and infarct size.

Time-efficient black blood RCA wall imaging at 3T using improved motion sensitized driven equilibrium (iMSDE): feasibility and reproducibility.

BACKGROUND: The aim of this study was to explore the feasibility and reproducibility of a time-efficient coronary vessel wall measurement approach using an improved motion-sensitized driven equilibrium (iMSDE) pulse sequence. METHODOLOGY: In this study, the iMSDE pulse sequence was first optimized and then applied on a group of healthy volunteers (N = 10) to evaluate its feasibility of vessel wall visualization. The same technique was also applied on a separate group of volunteers (N = 19) for a reproducibility study by scanning the same subject in two separate sessions. The iMSDE sequence was found to provide good coronary vessel wall delineation. It was also found to provide reproducible coronary vessel wall diameter and thickness measurements in both proximal and middle segments of the right coronary artery. CONCLUSION: The feasibility and reproducibility of iMSDE based coronary vessel wall imaging were demonstrated for the first time, paving the way for further testing in a clinical environment for fast and accurate coronary artery disease detection.

MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course.

OBJECTIVES: The purpose of this study was to test the lipid depletion hypothesis and to establish the time course of change in carotid plaque morphology and composition during lipid therapy using high-resolution magnetic resonance imaging (MRI). BACKGROUND: Lipid therapy is thought to improve plaque stability and reduce cardiovascular events by targeting the plaque rupture risk features such as large lipid core, thin fibrous cap, and high level of inflammatory infiltrates. However, the plaque stabilizing process during lipid therapy has not been clearly demonstrated in humans and in vivo. METHODS: Subjects with coronary or carotid artery disease, apolipoprotein B ≥120 mg/dl, and lipid treatment history <1 year, were randomly assigned to atorvastatin monotherapy or to atorvastatin-based combination therapies with appropriate placebos for 3 years. All subjects underwent high-resolution, multicontrast bilateral carotid MRI scans at baseline and annually for 3 years. All images were analyzed for quantification of wall area and plaque composition blinded to therapy, laboratory results, and clinical course. RESULTS: After 3 years of lipid therapy, the 33 subjects with measurable lipid-rich necrotic core (LRNC) at baseline had a significant reduction in plaque lipid content: LRNC volume decreased from 60.4 ± 59.5 mm(3) to 37.4 ± 69.5 mm(3) (p < 0.001) and %LRNC (LRNC area/wall area in the lipid-rich regions) from 14.2 ± 7.0% to 7.4 ± 8.2% (p < 0.001). The time course showed that %LRNC decreased by 3.2 (p < 0.001) in the first year, by 3.0 (p = 0.005) in the second year, and by 0.91 (p = 0.2) in the third year. Changes in LRNC volume followed the same pattern. Percent wall volume (100 × wall/outer wall, a ratio of volumes) in the lipid-rich regions significantly decreased from 52.3 ± 8.5% to 48.6 ± 9.7% (p = 0.002). Slices containing LRNC had significantly more percent wall volume reduction than those without (-4.7% vs. -1.4%, p = 0.02). CONCLUSIONS: Intensive lipid therapy significantly depletes carotid plaque lipid. Statistically significant plaque lipid depletion is observed after 1 year of treatment and continues in the second year, and precedes plaque regression. (Using Magnetic Resonance Imaging to Evaluate Carotid Artery Plaque Composition in People Receiving Cholesterol-Lowering Medications [The CPC Study]; NCT00715273).