Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014-2021. The utility of the previously defined total SIPAT cut-off (<21 [excellent/good candidates] vs ≥21 [minimally acceptable/high risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT score and LT waitlisting outcomes. Youden's J statistic was used to identify the optimal SIPAT cut-off for MASLD patients. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had SIPAT score ≥21. Patients with SIPAT score ≥21 had higher hemoglobin A1c compared to patients with lower psychosocial risk (median (IQR): 7.8 (6.0-9.7) vs 6.6 (5.8, 7.9); p=0.04). There were no other differences in metabolic comorbidities between SIPAT groups. Increasing SIPAT score was associated with decreased odds of listing (OR: 0.82 per five-point increase; p=0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cut-off in this population, resulting in an adjusted OR for listing of 0.53 vs SIPAT <12 (p=0.001). In this large cohort of MASLD patients evaluated for LT, few patients met the previously defined high SIPAT cut-off for transplant suitability. Nevertheless, increasing SIPAT score was associated with waitlist outcome. Our suggested SIPAT cut-off of ≥12 for MASLD patients warrants further external validation using data from other centers.

Ultrasound evaluation of intraluminal magnets in an ex vivo model.

PURPOSE: The management of foreign body ingestion proves to be a challenge. Magnets pose a unique set of risks when ingested due to their attractive forces and subsequent risk of adherence, pressure necrosis, and perforation complications. Radiographs only provide a limited snapshot in the setting of multiple magnet ingestion when the risk of complication is highest. We hypothesize that abdominal ultrasound (US) has the potential to supplement radiographs in assessing ingested magnets by determining the presence of bowel loop entrapment and of any extraluminal fluid. METHODS: We recreated various scenarios of magnet configurations using animal cadaveric bowel models. X-ray and US images were obtained in various bowel-magnet orientations. RESULTS: We identified several key US features to suggest bowel wall tethering. These include direct visualization of bowel wall entrapment between magnets (what we term the "dangerous V sign"), anti-dependent positions of the magnets, and inability to separate loops of bowel with compression. CONCLUSION: These findings could potentially provide valuable information when directing the urgency of intervention in foreign body ingestion. Ultrasound may supplement and improve the current guidelines in management of magnet ingestion.

Arteriolar dysgenesis in ischemic-regenerating skeletal muscle revealed by automated micromorphometry, computational modeling, and perfusion analysis.

Rebuilding the local vasculature is central to restoring the health of muscles subjected to ischemic injury. Arteriogenesis yields remodeled collateral arteries that circumvent the obstruction, and angiogenesis produces capillaries to perfuse the regenerating myofibers. However, the vital intervening network of arterioles that feed the regenerated capillaries is poorly understood and is an investigative challenge. We used machine learning and automated micromorphometry to quantify the arteriolar landscape in distal hindlimb muscles in mice that have regenerated after femoral artery excision. Assessment of 1,546 arteriolar sections revealed a striking (>2-fold) increase in arteriolar density in regenerated muscle 14 and 28 days after ischemic injury. Lumen caliber was initially similar to that of control arterioles but after 4 wk lumen area was reduced by 46%. In addition, the critical smooth muscle layer was attenuated throughout the arteriolar network, across a 150- to 5-µm diameter range. To understand the consequences of the reshaped distal hindlimb arterioles, we undertook computational flow modeling, which revealed blunted flow augmentation. Moreover, impaired flow reserve was confirmed in vivo by laser-Doppler analyses of flow in response to directly applied sodium nitroprusside. Thus, in hindlimb muscles regenerating after ischemic injury, the arteriolar network is amplified, inwardly remodels, and is diffusely undermuscularized. These defects and the associated flow restraints could contribute to the deleterious course of peripheral artery disease and merit attention when considering therapeutic innovations.NEW & NOTEWORTHY We report a digital pipeline for interrogating the landscape of arterioles in mouse skeletal muscle, using machine learning and automated micromorphometry. This revealed that in muscle regenerating after ischemic injury, the arteriolar density is increased but lumen caliber and smooth muscle content are reduced. Computational modeling and experimental validation reveal this arteriolar network to be functionally compromised, with diminished microvascular flow reserve.

Systematic Interrogation of Angiogenesis in the Ischemic Mouse Hind Limb: Vulnerabilities and Quality Assurance.

OBJECTIVE: There has been little success in translating preclinical studies of mouse hind limb ischemia into benefit for patients with peripheral artery disease. Using systematic strategies, we sought to define the injury and angiogenesis landscapes in mice subjected to hind limb ischemia and ascertain whether published studies to date have used an analysis strategy concordant with these data. Approach and Results: Maps of ischemic injury were generated from 22 different hind limb muscles and 33 muscle territories in 12-week-old C57BL/6 mice, based on loss or centralization of myofiber nuclei. Angiogenesis was similarly mapped based on CD (cluster of differentiation) 31-positive capillary content. Only 10 of 33 muscle territories displayed consistent muscle injury, with the distal anterior hind limb muscles most reliably injured. Angiogenesis was patchy and exclusively associated with zones of regenerated muscle (central nuclei). Angiogenesis was not observed in normal appearing muscle, necrotic muscle, or injury border zones. Systematic review of mouse hind limb angiogenesis studies identified 5147 unique publications, of which 509 met eligibility criteria for analysis. Only 7% of these analyzed manuscripts evaluated angiogenesis in distal anterior hind limb muscles and only 15% consistently examined for angiogenesis in zones of muscle regeneration. CONCLUSIONS: In 12-week C57BL/6 mice, angiogenesis postfemoral artery excision proceeds exclusively in zones of muscle regeneration. Only a minority of studies to date have analyzed angiogenesis in regions of demonstrably regenerating muscle or in high-likelihood territories. Quality assurance standards, informed by the atlas and mapping data herein, could augment data reliability and potentially help translate mouse hind limb ischemia studies to patient care.

The "Missing" Bicarbonate in CO2 Chemisorption Reactions on Solid Amine Sorbents.

We have identified a hydrated bicarbonate formed by chemisorption of 13CO2 on both dimethylaminopropylsilane (DMAPS) and aminopropylsilane (APS) pendant molecules grafted on SBA-15 mesoporous silica. The most commonly used sequence in solid-state NMR, 13C CPMAS, failed to detect bicarbonate in these solid amine sorbent samples; here, we have employed a Bloch decay ("pulse-acquire") sequence (with 1H decoupling) to detect such species. The water that is present contributes to the dynamic motion of the bicarbonate product, thwarting CPMAS but enabling direct 13C detection by shortening the spin-lattice relaxation time. Since solid-state NMR plays a major role in characterizing chemisorption reactions, these new insights that allow for the routine detection of previously elusive bicarbonate species (which are also challenging to observe in IR spectroscopy) represent an important advance. We note that employing this straightforward NMR technique can reveal the presence of bicarbonate that has often otherwise been overlooked, as demonstrated in APS, that has been thought to only contain adsorbed CO2 as carbamate and carbamic acid species. As in other systems (e.g., proteins), dynamic species that sample multiple environments tend to broaden as their motion is frozen out. Here, we show two distinct bicarbonate species upon freezing, and coupling to different protons is shown through preliminary 13C-1H HETCOR measurements. This work demonstrates that bicarbonates have likely been formed in the presence of water but have gone unobserved by NMR due to the nature of the experiments most routinely employed, a perspective that will transform the way the sorption community will view CO2 capture by amines.

Silica-Supported Sterically Hindered Amines for CO2 Capture.

Most studies exploring the capture of CO2 on solid-supported amines have focused on unhindered amines or alkylimine polymers. It has been observed in extensive solution studies that another class of amines, namely sterically hindered amines, can exhibit enhanced CO2 capacity when compared to their unhindered counterparts. In contrast to solution studies, there has been limited research conducted on sterically hindered amines on solid supports. In this work, one hindered primary amine and two hindered secondary amines are grafted onto mesoporous silica at similar amine coverages, and their adsorption performances are investigated through fixed bed breakthrough experiments and thermogravimetric analysis. Furthermore, chemisorbed CO2 species formed on the sorbents under dry and humid conditions are elucidated using in situ Fourier-transform infrared spectroscopy. Ammonium bicarbonate formation and enhancement of CO2 adsorption capacity is observed for all supported hindered amines under humid conditions. Our experiments in this study also suggest that chemisorbed CO2 species formed on supported hindered amines are weakly bound, which may lead to reduced energy costs associated with regeneration if such materials were deployed in a practical separation process. However, overall CO2 uptake capacities of the solid supported hindered amines are modest compared to their solution counterparts. The oxidative and thermal stabilities of the supported hindered amine sorbents are also assessed to give insight into their operational lifetimes.

Probing Metal-Organic Framework Design for Adsorptive Natural Gas Purification.

Parent and amine-functionalized analogues of metal-organic frameworks (MOFs), UiO-66(Zr), MIL-125(Ti), and MIL-101(Cr), were evaluated for their hydrogen sulfide (H2S) adsorption efficacy and post-exposure acid gas stability. Adsorption experiments were conducted through fixed-bed breakthrough studies utilizing multicomponent 1% H2S/99% CH4 and 1% H2S/10% CO2/89% CH4 natural gas simulant mixtures. Instability of MIL-101(Cr) materials after H2S exposure was discovered through powder X-ray diffraction and porosity measurements following adsorbent pelletization, whereas other materials retained their characteristic properties. Linker-based amine functionalities increased H2S breakthrough times and saturation capacities from their parent MOF analogues. Competitive CO2 adsorption effects were mitigated in mesoporous MIL-101(Cr) and MIL-101-NH2(Cr), in comparison to microporous UiO-66(Zr) and MIL-125(Ti) frameworks. This result suggests that the installation of H2S binding sites in large-pore MOFs could potentially enhance H2S selectivity. In situ Fourier transform infrared measurements in 10% CO2 and 5000 ppm H2S environments suggest that framework hydroxyl and amine moieties serve as H2S physisorption sites. Results from this study elucidate design strategies and stability considerations for engineering MOFs in sour gas purification applications.

15N Solid State NMR Spectroscopic Study of Surface Amine Groups for Carbon Capture: 3-Aminopropylsilyl Grafted to SBA-15 Mesoporous Silica.

Materials composed of high-porosity solid supports, such as SBA-15, containing amine-bearing moieties inside the pores, such as 3-aminopropylsilane (APS), are envisioned for carbon dioxide capture; solid-state 15N NMR can be highly informative for studying chemisorption reactions. Two 15N-enriched samples with different APS loadings were studied to probe the identity of the pendant molecules and structure of the chemisorbed CO2 species. 15N cross-polarization magic-angle spinning NMR provides unique information about the amines, whether they are rigid or dynamic, by measuring contact time curves and rotating frame, T1ρ(15N), relaxation. Both carbamate and carbamic acid are formed; carbamic acid is shown to be less stable than carbamate. After desorption, a steady state for the chemisorbed reaction product is reached, leaving behind carbamate. 15N NMR monitors the evolution of the species over time. During desorption, APS is regenerated, but the ammonium propylsilane intensity does not change, leading us to conclude that carbamic acid desorbs, while carbamate (to which ammonium propylsilane is ion paired) persists. A secondary ditehtered amine present does not react with CO2, and we posit this may be due to its rigidity. These findings demonstrate the versatility of solid-state NMR to provide information about these complex CO2 reactions with solid amine sorbents.

Spectroscopic Characterization of Adsorbed 13CO2 on 3-Aminopropylsilyl-Modified SBA15 Mesoporous Silica.

Multiple chemisorption products are found from the interaction of CO2 with the solid-amine sorbent, 3-aminopropyl silane (APS), bound to mesoporous silica (SBA15) using solid-state NMR and FTIR spectroscopy. We employed a combination of both 15N{13C} rotational-echo double-resonance (REDOR) NMR and 13C{15N} REDOR to determine the chemical identity of these products. 15N{13C} REDOR measurements are consistent with a single 13C-15N pair and distance of 1.45 Å. In contrast, both 13C{15N} REDOR and 13C CPMAS are consistent with multiple 13C products. 13C CPMAS shows two neighboring resonances, whose chemical shifts are consistent with carbamate (at 165 ppm) and carbamic acid. The 13C{15N} REDOR experiments resonant at 165 ppm show an incomplete buildup of the REDOR data to ∼90% of the expected maximum. We conclude this 10% missing intensity corresponds to a 13C NMR species that resonates at the identical chemical shift but that is not in dipolar contact with 15N. These data are consistent with the presence of bicarbonate, HCO3-, since it is commonly observed at ∼165 ppm and lacks 15N for dipolar coupling.

Emerging drugs and therapeutics for systemic sclerosis.

INTRODUCTION: Treatment of systemic sclerosis (SSc) is challenging despite advances in medical therapeutics for other rheumatologic diseases. Significant disease modifying therapy is lacking for most patients with SSc, due to the heterogeneous multisystem nature of SSc and its complex pathophysiology. The emergence of organ based management strategies has provided guidance in patient care as well as research and drug development. Areas covered: Design and development of new compounds focused on the underlying fibrotic disease processes have been sparse. Therefore, organ based strategies with targeted approaches have been directed towards the most devastating and life threatening features of systemic sclerosis. These include pulmonary arterial hypertension, interstitial lung disease, peripheral vasculopathy and skin thickening. In this context, new treatment regimens using older drugs as well as discovery of novel compounds based on recent insights of the disease pathophysiology are discussed. Expert opinion: Systemic sclerosis is a heterogeneous rare disease that carries a high burden of morbidity and mortality. Organ based management strategies have improved the natural history of systemic sclerosis using targeted interventions or strategies, particularly vascular features. However, more research is required to better understand disease mechanisms, including an ultimate unifying pathway that explains the multisystem nature of systemic sclerosis.

Improved microcalcification visualization using dual-energy digital mammography.

BACKGROUND: Dual-energy digital mammography (DEDM), involving a combination of high-energy (HE) and low-energy (LE) images, has been investigated as offering a potential improvement in microcalcification detection obscured by overlapping tissue structures. PURPOSE: To explore the possibility to improve detection of microcalcifications using the DEDM technique. MATERIAL AND METHODS: Three DEDM protocols were performed by adjusting the effective tube current time product (mAs) of LE image at the same (100%), one half (50%), and one-quarter (25%) of that used in HE image acquisition, named DEDM100%, DEDM50%, and DEDM25%, respectively. A single-energy digital mammography (SEDM) method was also used as a control. A total of 525 regions of interest (ROIs) were used to compare the performance of the DEDM to that of SEDM using free-response receiver-operating characteristic (FROC) and areas under the FROC curve (Az). RESULTS: All DEDM protocols ranked significantly higher than the SEDM method (P < 0.001). The true-positive fraction was 0.90 for an average of 0.017-0.042 false-positive per image using the DEDM100%, 0.017-0.114 using the DEDM50%, 0.021-0.148 using the DEDM25%, and 0.134-0.422 using the SEDM. The estimated Az values were 0.915-0.940, 0.867-0.935, 0.824-0.930, and 0.567-0.673, respectively. CONCLUSION: The DEDM50% protocol provided a trade-off benefit between accurate microcalcification detectability and radiation dose for any tissue density. Therefore, the DEDM50% has the potential to minimize excess radiation dose without a negative impact on image quality which could improve earlier diagnosis of breast cancer.

Endocytosis in cancer and cancer therapy.

Endocytosis is a complex process whereby cell surface proteins, lipids and fluid from the extracellular environment are packaged, sorted and internalized into cells. Endocytosis is also a mechanism of drug internalization into cells. There are multiple routes of endocytosis that determine the fate of molecules, from degradation in the lysosomes to recycling back to the plasma membrane. The overall rates of endocytosis and temporal regulation of molecules transiting through endocytic pathways are also intricately linked with signalling outcomes. This process relies on an array of factors, such as intrinsic amino acid motifs and post-translational modifications. Endocytosis is frequently disrupted in cancer. These disruptions lead to inappropriate retention of receptor tyrosine kinases on the tumour cell membrane, changes in the recycling of oncogenic molecules, defective signalling feedback loops and loss of cell polarity. In the past decade, endocytosis has emerged as a pivotal regulator of nutrient scavenging, response to and regulation of immune surveillance and tumour immune evasion, tumour metastasis and therapeutic drug delivery. This Review summarizes and integrates these advances into the understanding of endocytosis in cancer. The potential to regulate these pathways in the clinic to improve cancer therapy is also discussed.

Predicting Septic Shock After Emergent Ureteral Stenting in Stone-Related Obstruction and Presumed Infections.

Introduction: Systemic inflammatory response syndrome (SIRS) criteria have long been used to predict septic shock. The sequential organ failure assessment and quick sequential organ failure assessment (qSOFA) scores have been suggested to be more accurate predictors. This study aims to compare SIRS and qSOFA for predicting of septic shock in the setting of retrograde ureteral stenting for obstructing stones and concomitant urinary tract infection. Methods: A retrospective review of records at two centers of consecutive patients was performed. Patients with unilateral ureteral obstruction by a stone who underwent ureteral stent placement and suspicion of urinary tract infection were identified. Primary endpoints were SIRS and qSOFA positive scores, intensive care unit admission, and vasopressor requirements. Results: A total of 187 patients were included. SIRS criteria were met in 103 patients (55.1%) and in 30 patients who experienced septic shock. qSOFA criteria were met for 24 patients (12.8%) and in 18 patients who experienced septic shock. Specificity for postoperative septic shock was significantly higher for qSOFA than for SIRS criteria (75 vs 29.1%, McNemar test p < 0.001). Both SIRS and qSOFA had significant areas under the curve (AUC), qSOFA had a fair AUC of 0.750, p = 0.001, whereas SIRS had a poor AUC of 0.659, p = 0.008. Univariate logistic regression of SIRS and qSOFA for septic shock showed: qSOFA (odds ratio [OR] 46 [0.25-228], p = 0.001) and SIRS (OR 2.29 [0.716-7.37], p = 0.162). Conclusion: Although SIRS offers higher sensitivity, qSOFA score may offer advantages over SIRS criteria in evaluation of risk for septic shock for patients who present with obstructing ureteral stone and urinary tract infection.

Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

PURPOSE: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. EXPERIMENTAL DESIGN: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. RESULTS: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. CONCLUSIONS: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Interstitial myocardial fibrosis assessed as extracellular volume fraction with low-radiation-dose cardiac CT.

PURPOSE: To develop a cardiac computed tomographic (CT) method with which to determine extracellular volume (ECV) fraction, with cardiac magnetic resonance (MR) imaging as the reference standard. MATERIALS AND METHODS: Study participants provided written informed consent to participate in this institutional review board-approved study. ECV was measured in healthy subjects and patients with heart failure by using cardiac CT and cardiac MR imaging. Paired Student t test, linear regression analysis, and Pearson correlation analysis were used to determine the relationship between cardiac CT and MR imaging ECV values and clinical parameters. RESULTS: Twenty-four subjects were studied. There was good correlation between myocardial ECV measured at cardiac MR imaging and that measured at cardiac CT (r = 0.82, P < .001). As expected, ECV was higher in patients with heart failure than in healthy control subjects for both cardiac CT and cardiac MR imaging (P = .03, respectively). For both cardiac MR imaging and cardiac CT, ECV was positively associated with end diastolic and end systolic volume and inversely related to ejection fraction (P < .05 for all). Mean radiation dose was 1.98 mSv ± 0.16 (standard deviation) for each cardiac CT acquisition. CONCLUSION: ECV at cardiac CT and that at cardiac MR imaging showed good correlation, suggesting the potential for myocardial tissue characterization with cardiac CT.

Feasibility study for the improvement of microcalcification visualization in different breast thicknesses and tissue components using a dual-energy approach in digital mammography.

OBJECTIVE: The purpose of this study was to improve detectability of microcalcifications using a dual-energy digital mammographic (DEDM) technique. METHODS: Slabs of uniform breast-equivalent plastic and an additional plate were used to mimic various breast thicknesses, from 3 to 7 cm, and to simulate microcalcification with diameters from 0.16 to 0.39 mm. Free-response receiver operating characteristics and area under the curves (Az) were used to evaluate the sensitivity of detecting microcalcifications using the DEDM compared with using the conventional single-energy digital mammography (SEDM). RESULTS: The mean number of false-positives per image was 0.0198 (Az = 0.956 ± 0.027) using DEDM compared with 0.292 (Az = 0.681 ± 0.235) using SEDM. A lower radiation dose could be possibly obtained for the DEDM technique with a thickness of less than 5 cm compared with the SEDM with a thickness larger than 5 cm. CONCLUSIONS: Microcalcifications could be more accurately and efficiently detected using the DEDM, which might bring reliable and promising applications on early computer-aided diagnosis of breast cancer.

Incidental finding of lung hernia in a patient with a remote history of empyema status post video-assisted thoracoscopic surgery.

Lung hernia, the protrusion of pulmonary tissue outside of the thoracic cage, is a rare radiologic finding. The exact incidence of this condition is not well documented. The etiology is either secondary to underlying congenital conditions which weaken the supporting structures of the thoracic wall or more commonly, post-surgical changes. In this report, we describe the case of a 58-year-old male trauma patient who was involved in a motor vehicle collision. Computed tomography of the head, neck, body, and upper extremities was negative for acute injury, but an incidental left-sided herniation of the lingula between the fifth and sixth intercostal spaces was identified. Computed tomography is superior for identifying imaging lung herniations as chest radiographs may not visualize the defect. Upon further investigation, the patient had a remote history of pneumonia complicated by empyema treated by video-assisted thoracoscopic surgery (VATS). This history, coupled with the absence of traumatic injury to the thorax as well as the presence of pulmonary scarring suggests that the lung herniation was likely chronic and secondary to the VATS procedure. The patient was discharged home without surgical intervention. Asymptomatic lung herniations are typically managed conservatively, but patients and physicians should be aware of the risk of lung hernia after VATS as well as associated complications including strangulation or pulmonary infarct.

Myocardial T1 and extracellular volume fraction mapping at 3 tesla.

BACKGROUND: To compare 11 heartbeat (HB) and 17 HB modified lock locker inversion recovery (MOLLI) pulse sequence at 3T and to establish preliminary reference values for myocardial T1 and the extracellular volume fraction (ECV). METHODS: Both phantoms and normal volunteers were scanned at 3T using 11 HB and 17 HB MOLLI sequence with the following parameters: spatial resolution = 1.75 × 1.75 × 10 mm on a 256 × 180 matrix, TI initial = 110 ms, TI increment = 80 ms, flip angle = 35°, TR/TE = 1.9/1.0 ms. All volunteers were administered Gadolinium-DTPA (Magnevist, 0.15 mmol/kg), and multiple post-contrast MOLLI scans were performed at the same pre-contrast position from 3.5-23.5 minutes after a bolus contrast injection. Late gadolinium enhancement (LGE) images were also acquired 12-30 minutes after the gadolinium bolus. RESULTS: T1 values of 11 HB and 17 HB MOLLI displayed good agreement in both phantom and volunteers. The average pre-contrast myocardial and blood T1 was 1315 ± 39 ms and 2020 ± 129 ms, respectively. ECV was stable between 8.5 to 23.5 minutes post contrast with an average of 26.7 ± 1.0%. CONCLUSION: The 11 HB MOLLI is a faster method for high-resolution myocardial T1 mapping at 3T. ECV fractions are stable over a wide time range after contrast administration.

Regenerated Microvascular Networks in Ischemic Skeletal Muscle.

Skeletal muscle is the largest organ in humans. The viability and performance of this metabolically demanding organ are exquisitely dependent on the integrity of its microcirculation. The architectural and functional attributes of the skeletal muscle microvasculature are acquired during embryonic and early postnatal development. However, peripheral vascular disease in the adult can damage the distal microvasculature, together with damaging the skeletal myofibers. Importantly, adult skeletal muscle has the capacity to regenerate. Understanding the extent to which the microvascular network also reforms, and acquires structural and functional competence, will thus be critical to regenerative medicine efforts for those with peripheral artery disease (PAD). Herein, we discuss recent advances in studying the regenerating microvasculature in the mouse hindlimb following severe ischemic injury. We highlight new insights arising from real-time imaging of the microcirculation. This includes identifying otherwise hidden flaws in both network microarchitecture and function, deficiencies that could underlie the progressive nature of PAD and its refractoriness to therapy. Recognizing and overcoming these vulnerabilities in regenerative angiogenesis will be important for advancing treatment options for PAD.

Flat Panel Detector c-Arms Are Associated with Dramatically Reduced Radiation Exposure During Ureteroscopy and Produce Superior Images.

Background: We wished to determine whether newly available flat panel detector (FPD) c-arms were (1) associated with lower radiation dose during ureteroscopy (URS) than conventional image intensifier (CII) c-arms and (2) to compare fluoroscopic image quality between the units. Materials and Methods: We retrospectively reviewed 44 consecutive patients undergoing URS at a pediatric hospital, with c-arms assigned by availability in the operating room. We performed dosimetry experiments using the same c-arms on standard phantoms. Results: Patient and case characteristics did not differ significantly between the two groups of patients. The median dose in the FPD group was less than a quarter of the dose in the CII group, 0.48 [0.42, 0.97] mGy vs 2.2 [1.1, 3.8] mGy, p < 0.0001. The FPD dose remained at less than one-third of the CII dose accounting for any difference in fluoroscopy time, and remained significant in a multivariate model including fluoroscopy time and patient weight (ß = 2.4, p = 0.007). Phantom studies showed higher image quality for FPDs at all simulated patient sizes, even at lower radiation doses. Conclusions: This is the first report comparing radiation dose from c-arms of image intensifiers and FPDs in adults or children. Use of an FPD during URS was associated with a substantially decreased absorbed dose for patients while simultaneously improving image quality.