Noncontact speckle contrast diffuse correlation tomography of blood flow distributions in tissues with arbitrary geometries.

A noncontact electron multiplying charge-coupled-device (EMCCD)-based speckle contrast diffuse correlation tomography (scDCT) technology has been recently developed in our laboratory, allowing for noninvasive three-dimensional measurement of tissue blood flow distributions. One major remaining constraint in the scDCT is the assumption of a semi-infinite tissue volume with a flat surface, which affects the image reconstruction accuracy for tissues with irregular geometries. An advanced photometric stereo technique (PST) was integrated into the scDCT system to obtain the surface geometry in real time for image reconstruction. Computer simulations demonstrated that a priori knowledge of tissue surface geometry is crucial for precisely reconstructing the anomaly with blood flow contrast. Importantly, the innovative integration design with one single-EMCCD camera for both PST and scDCT data collection obviates the need for offline alignment of sources and detectors on the tissue boundary. The in vivo imaging capability of the updated scDCT is demonstrated by imaging dynamic changes in forearm blood flow distribution during a cuff-occlusion procedure. The feasibility and safety in clinical use are evidenced by intraoperative imaging of mastectomy skin flaps and comparison with fluorescence angiography.

Dermal Regenerative Template as a Cost-Effective Alternative for Complex Scalp Reconstruction.

BACKGROUND: Use of dermal regeneration template (DRT) is well documented in the literature for complex wounds ranging from the scalp, trunk, and lower extremity. METHODS: A retrospective cohort study was performed of the use of dermal regeneration template and skin grafting. A literature review was performed of all studies where DRT was used for scalp reconstruction. RESULTS: Patients in the DRT cohort had an average age of 70, with wounds averaging 108 cm in size. These patients also had a relatively low rate of complications (0.4), a short hospital stay (average 2 days), and a relatively short operating room time (114 minutes). CONCLUSION: This study demonstrates dermal regeneration template to be an effective and reliable option for soft tissue reconstruction with minimal morbidity and complications in patients with extensive medical comorbidities. Emerging applications include radiation exposure and hypercoaguable states.

A Novel Noncontact Diffuse Correlation Spectroscopy Device for Assessing Blood Flow in Mastectomy Skin Flaps: A Prospective Study in Patients Undergoing Prosthesis-Based Reconstruction.

A new advanced technology, noncontact diffuse correlation spectroscopy, has been recently developed for the measurement of tissue blood flow through analyzing the motions of red blood cells in deep tissues. This technology is portable, inexpensive, and noninvasive, and can measure up to 1.5-cm tissue depth. In this prospective study, the authors aimed to explore the use of this novel device in the prediction of mastectomy skin flap necrosis. The noncontact diffuse correlation spectroscopy device was used to measure mastectomy skin flap flow in patients undergoing mastectomy and immediate implant-based breast reconstruction before and immediately after mastectomy, and after placement of the prosthesis. Patients were tracked for the development of complications, including skin necrosis and the need for further surgery. Nineteen patients were enrolled in the study. Four patients (21 percent) developed skin necrosis, one of which required additional surgery. The difference in relative blood flow levels immediately after mastectomy in patients with or without necrosis was statistically significant, with values of 0.27 ± 0.11 and 0.66 ± 0.22, respectively (p = 0.0005). Relative blood flow measurements immediately after mastectomy show a significant high accuracy in prediction of skin flap necrosis, with an area under the receiver operating characteristic curve of 0.95 (95 percent confidence interval, 0.81 to 1). The noncontact diffuse correlation spectroscopy device is a promising tool that provides objective information regarding mastectomy skin flap viability intraoperatively, allowing surgeons early identification of those compromised and ischemic flaps with the hope of potentially salvaging them. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Symptomatic Nonsyndromic Pancarpal Coalition: Report of a Rare Case and Review of the Literature.

Carpal coalition, the union of 2 or more carpal bones, can be congenital or acquired. Congenital, nonsyndromic carpal coalition usually presents in otherwise healthy individuals. The most common coalition is between the lunate and the triquetrum, followed by the capitate and the hamate. Pancarpal coalition, or coalition of all or most of the bones of the carpus, is an extremely rare finding and usually occurs as part of a syndrome. We present a nonsyndromic case of this rare entity, in a 28-year-old woman of West African descent, with symptoms of left hand and wrist pain. Our literature review revealed only 1 other reported case of isolated, nonsyndromic symptomatic pancarpal coalition.

Hearing loss in syndromic craniosynostoses: otologic manifestations and clinical findings.

OBJECTIVE: This review addresses hearing loss as it occurs and has been reported in Muenke syndrome as well as six additional FGFR related craniosynostosis syndromes (Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, Beare-Stevenson syndrome, Crouzon syndrome with acanthosis nigricans, and Jackson-Weiss syndrome. DATA SOURCES: Pub-Med, Medline, Cochrane Database, Science Direct, NLM Catalog. REVIEW METHODS: A Medline search was conducted to find all reported cases of the 7 FGFR related syndromic craniosynostosis. Special attention was paid to literature that reported hearing findings and the audiology literature. RESULTS: Hearing loss occurs in variable percentage as a component part of all FGFR related craniosynostosis syndromes. Our literature review revealed the following incidences of hearing loss in FGFR craniosynostoses: 61% in Muenke syndrome, 80% in Apert Syndrome, 92% in Pfeiffer syndrome, 74% in Crouzon syndrome, 68% in Jackson Weiss syndrome, 4% in Beare Stevenson syndrome and 14% in Crouzon syndrome with Acanthosis Nigricans. The majority of the hearing loss is a conductive hearing loss, with the exception of Muenke syndrome where the majority of patients have a sensorineural hearing loss and Crouzon syndrome where almost half of patients have a pure or component of sensorineural hearing loss. CONCLUSION: This manuscript presents a diagnostic and management algorithm for patients with syndromic craniosynostosis. It will aid clinicians in treating these patients and further, the recognition of a possible syndrome in patients with hearing loss who also have syndromic features.

Impact of genetics on the diagnosis and clinical management of syndromic craniosynostoses.

PURPOSE: More than 60 different mutations have been identified to be causal in syndromic forms of craniosynostosis. The majority of these mutations occur in the fibroblast growth factor receptor 2 gene (FGFR2). The clinical management of syndromic craniosynostosis varies based on the particular causal mutation. Additionally, the diagnosis of a patient with syndromic craniosynostosis is based on the clinical presentation, signs, and symptoms. The understanding of the hallmark features of particular syndromic forms of craniosynostosis leads to efficient diagnosis, management, and long-term prognosis of patients with syndromic craniosynostoses. METHODS: A comprehensive literature review was done with respect to the major forms of syndromic craniosynostosis and additional less common FGFR-related forms of syndromic craniosynostosis. Additionally, information and data gathered from studies performed in our own investigative lab (lab of Dr. Muenke) were further analyzed and reviewed. A literature review was also performed with regard to the genetic workup and diagnosis of patients with craniosynostosis. RESULTS: Patients with Apert syndrome (craniosynostosis syndrome due to mutations in FGFR2) are most severely affected in terms of intellectual disability, developmental delay, central nervous system anomalies, and limb anomalies. All patients with FGFR-related syndromic craniosynostosis have some degree of hearing loss that requires thorough initial evaluations and subsequent follow-up. CONCLUSIONS: Patients with syndromic craniosynostosis require management and treatment of issues involving multiple organ systems which span beyond craniosynostosis. Thus, effective care of these patients requires a multidisciplinary approach.

Phenotype profile of a genetic mouse model for Muenke syndrome.

PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation. Muenke syndrome is characterized by coronal suture synostosis, midface hypoplasia, subtle limb anomalies, and hearing loss. However, the spectrum of clinical presentation continues to expand. To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes. CONCLUSIONS: FgfR3 (P244R) mutant mice show premature fusion of facial sutures, premaxillary and/or zygomatic sutures, but rarely the coronal suture. The mice also lack the typical limb phenotype. On the other hand, the mutant mice display maxillary retrusion in association with a shortening of the anterior cranial base and a premature closure of intersphenoidal and spheno-occipital synchondroses, resembling human midface hypoplasia. In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients. It is caused by a defect in the mechanism of cell fate determination in the organ of Corti. The mice also express phenotypes that have not been previously described in humans, such as reduced cortical bone thickness, hypoplastic trabecular bone, and defective temporomandibular joint structure. Therefore, the FgfR3 (P244R) mouse provides an excellent opportunity to study disease mechanisms of some classical phenotypes of Muenke syndrome and to test novel therapeutic strategies. The mouse model can also be further explored to discover previously unreported yet potentially significant phenotypes of Muenke syndrome.

Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association.

VACTERL association, a relatively common condition with an incidence of approximately 1 in 20,000 -35,000 births, is a non-random association of birth defects that includes vertebral defects (V), anal atresia (A), cardiac defects (C), tracheo-esophageal fistula (TE), renal anomalies (R) and limb malformations (L). Although the etiology is unknown in the majority of patients, there is evidence that it is causally heterogeneous. Several studies have shown evidence for inheritance in VACTERL, implying a role for genetic loci. Recently, patients with component features of VACTERL and a lethal developmental pulmonary disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), were found to harbor deletions or mutations affecting FOXF1 and the FOX gene cluster on chromosome 16q24. We investigated this gene through direct sequencing and high-density SNP microarray in 12 patients with VACTERL association but without ACD/MPV. Our mutational analysis of FOXF1 showed normal sequences and no genomic imbalances affecting the FOX gene cluster on chromosome 16q24 in the studied patients. Possible explanations for these results include the etiologic and clinical heterogeneity of VACTERL association, the possibility that mutations affecting this gene may occur only in more severely affected individuals, and insufficient study sample size.