Collagen remodeling is an integral part of tissue development, maintenance, and regeneration, but excessive remodeling is associated with various pathologic conditions. The ability to target collagens undergoing remodeling could lead to new diagnostics and therapeutics as well as applications in regenerative medicine; however, such collagens are often degraded and denatured, making them difficult to target with conventional approaches. Here, we present caged collagen mimetic peptides (CMPs) that can be phototriggered to fold into triple helix and bind to collagens denatured by heat or by matrix metalloproteinase (MMP) digestion. Peptidebinding assays indicate that the binding is primarily driven by stereo-selective triple-helical hybridization between monomeric CMPs of high triple-helical propensity and denatured collagen strands. Photo-triggered hybridization allows specific staining of collagen chains in protein gels as well as photo-patterning of collagen and gelatin substrates. In vivo experiments demonstrate that systemically delivered CMPs can bind to collagens in bones, as well as prominently in articular cartilages and tumors characterized by high MMP activity. We further show that CMP-based probes can detect abnormal bone growth activity in a mouse model of Marfan syndrome. This is an entirely new way to target the microenvironment of abnormal tissues and could lead to new opportunities for management of numerous pathologic conditions associated with collagen remodeling and high MMP activity.A s the most abundant protein in mammals, collagens play a crucial role in tissue development and regeneration, and their structural or metabolic abnormalities are associated with debilitating genetic diseases and various pathologic conditions. Although collagen remodeling occurs during development and normal tissue maintenance, particularly for renewing tissues (e.g., bones), excess remodeling activity is commonly seen in tumors, arthritis, and many other chronic wounds. During collagen remodeling, large portions of collagens are degraded and denatured by proteolytic enzymes, which can be explored for diagnostic and therapeutic purposes. Since unstructured proteins are not ideal targets for rational drug design, library approaches have been employed to develop monoclonal antibody (1, 2) and peptide probes (3) that specifically bind to cryptic sites in collagen strands that become exposed when denatured. However, these probes suffer from poor pharmacokinetics (4), and/or low specificity, and binding affinity (5).We envisioned that triple helix, the hallmark structural feature of collagen, could provide a unique targeting mechanism for the denatured collagens. The triple helix is nearly exclusively seen in collagens except as small subdomains in a few noncollagen proteins (6). Considering its striking structural similarity to the DNA double helix in terms of multiplex formation by periodic interchain hydrogen bonds along the polymer backbone (6), we thought that a small peptide sequence with strong triple-helix prope...

Objective To characterize effects of age and physical activity level on cartilage thickness and T2 response immediately after running. Design Institutional review board approval was obtained and all subjects provided informed consent prior to study participation. Cartilage thickness and MRI T2 values of 22 marathon runners and 15 sedentary controls were compared before and after 30 minutes of running. Runner and control groups were stratified by age ≤ 45 and ≥ 46 years. Multi-echo (TR/TE 1500 ms/9 –109 ms) MR images obtained using a 3.0 T scanner were used to calculate thickness and T2 values from the central femoral and tibial cartilage. Baseline cartilage T2 values, and change in cartilage thickness and T2 values after running were compared between the four groups using 1-way ANOVA. Results After running MRI T2 values decreased in superficial femoral (2 ms to 4 ms) and tibial (1 ms to 3 ms) cartilage along with a decrease in cartilage thickness: (femoral: 4% to 8%, tibial: 0% to 12%). Smaller decrease in cartilage t2 values were observed in the middle zone of cartilage, and no change was observed in the deepest layer. There was no difference cartilage deformation or T2 response to running as a function of age or level of physical activity. Conclusions Running results in a measurable decrease in cartilage thickness and MRI T2 values of superficial cartilage consistent with greater compressibility of the superficial cartilage layer. Age and level of physical activity did not alter the T2 response to running.

Replacing femoral arterial access evaluations by DSA with fluoroscopy, utilizing lower pulse rates during fluoroscopy and roadmap guidance, and choosing variable frame rates for DSA are simple techniques that may be considered by operators in their clinical practices to lower radiation dose during cerebral angiography procedures.

OBJECTIVE Endovascular thrombectomy in patients with acute ischemic stroke caused by occlusion of the proximal anterior circulation arteries is superior to standard medical therapy. Stentriever thrombectomy with or without aspiration assistance was the predominant technique used in the 5 randomized controlled trials that demonstrated the superiority of endovascular thrombectomy. Other studies have highlighted the efficacy of a direct aspiration first-pass technique (ADAPT). METHODS To compare the angiographic and clinical outcomes of ADAPT versus stentriever thrombectomy in patients with emergent large vessel occlusions (ELVO) of the anterior intracranial circulation, the records of 134 patients who were treated between June 2012 and October 2015 were reviewed. RESULTS Within this cohort, 117 patients were eligible for evaluation. ADAPT was used in 47 patients, 20 (42.5%) of whom required rescue stentriever thrombectomy, and primary stentriever thrombectomy was performed in 70 patients. Patients in the ADAPT group were slightly younger than those in the stentriever group (63.5 vs 69.4 years; p = 0.04); however, there were no differences in the other baseline clinical or radiographic factors. Procedural time (54.0 vs 77.1 minutes; p < 0.01) and time to a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b/3 recanalization (294.3 vs 346.7 minutes; p < 0.01) were significantly lower in patients undergoing ADAPT versus stentriever thrombectomy. The rates of TICI 2b/3 recanalization were similar between the ADAPT and stentriever groups (82.9% vs 71.4%; p = 0.19). There were no differences in the rates of symptomatic intracranial hemorrhage or procedural complications. The rates of good functional outcome (modified Rankin Scale Score 0-2) at 90 days were similar between the ADAPT and stentriever groups (48.9% vs 41.4%; p = 0.45), even when accounting for the subset of patients in the ADAPT group who required rescue stentriever thrombectomy. CONCLUSIONS The present study demonstrates that ADAPT and primary stentriever thrombectomy for acute ischemic stroke due to ELVO are equivalent with respect to the rates of TICI 2b/3 recanalization and 90-day mRS scores. Given the reduced procedural time and time to TICI 2b/3 recanalization with similar functional outcomes, an initial attempt at recanalization with ADAPT may be warranted prior to stentriever thrombectomy.

OBJECTIVE Vascular malformations of the spine represent rare clinical entities with profound neurological implications. Previously reported studies on management strategies for spinal dural arteriovenous fistulas (sDAVFs) appeared before the advent of modern liquid embolic agents. Authors of the present study review their institutional experience with endovascularly and surgically treated sDAVFs. METHODS The authors performed a retrospective, observational, single-center case series on sDAVFs treated with endovascular embolization, microsurgical occlusion, or both between 2004 and 2013. The mode, efficacy, and clinical effect of treatment were evaluated. RESULTS Forty-seven patients with spinal arteriovenous malformations were evaluated using spinal angiography, which demonstrated 34 Type I sDAVFs (thoracic 20, lumbar 12, and cervical 2). Twenty-nine of the patients (85%) were male, and the median patient age was 63.3 years. Twenty patients underwent primary endovascular embolization (16 Onyx, 4 N-butyl cyanoacrylate [NBCA]), and 14 underwent primary surgical clipping. At a mean follow-up of 36 weeks, according to angiography or MR angiography, 5 patients treated with endovascular embolization demonstrated persistent arteriovenous shunting, whereas none of the surgically treated patients showed lesion persistence (p = 0.0237). Thirty patients (88%) experienced some resolution of their presenting symptoms (embolization 17 [85%], surgery 13 [93%], p = 1.00). CONCLUSIONS Microsurgical occlusion remains the most definitive treatment modality for sDAVFs, though modern endovascular techniques remain a viable option for the initial treatment of anatomically amenable lesions. Treatment of these lesions usually results in some clinical improvement.

This study confirms that the MRRC enhances the predictive accuracy of the RROC.

Low dose 3D-DSA protocols with preserved image quality are achievable, and can help reduce exposure of patients and operators to unnecessary radiation. The 5 s 0.24 μGy/f protocol generates one-third smaller radiation dose than the standard 5 s 0.36 μGy/f protocol without compromising diagnostic image quality or accuracy.

Diagnostic imaging plays an essential role in the evaluation of disease processes that affect the upper airway. Imaging allows for the localization and characterization of various conditions that are often occult on physical examination. Plain radiography maintains a limited role in airway evaluation, whereas advanced imaging modalities, including computed tomography and magnetic resonance imaging, have emerged as indispensable tools in patient evaluation. Common disease entities affecting the upper airway in the adult population, including trauma, infectious/inflammatory diseases, and neoplastic diseases, as well as other common pathologic conditions are reviewed in this article.