Hani S. Matloub

Resting-State Functional Connectivity of the Rat Brain

Regional‐specific average time courses of spontaneous fluctuations in blood oxygen level dependent (BOLD) MRI contrast at 9.4T in lightly anesthetized resting rat brain are formed, and correlation coefficients between time course pairs are interpreted as measures of connectivity. A hierarchy of regional pairwise correlation coefficients (RPCCs) is observed, with the highest values found in the thalamus and cortex, both intra‐ and interhemisphere, and lower values between the cortex and thalamus. Independent sensory networks are distinguished by two methods: data driven, where task activation defines regions of interest (ROI), and hypothesis driven, where regions are defined by the rat histological atlas. Success in these studies is attributed in part to the use of medetomidine hydrochloride (Domitor) for anesthesia. Consistent results in two different rat‐brain systems, the sensorimotor and visual, strongly support the hypothesis that resting‐state BOLD fluctuations are conserved across mammalian species and can be used to map brain systems. Magn Reson Med 59:1021–1029, 2008.

Osteogenesis in calvarial defects: contribution of the dura, the pericranium, and the surrounding bone in adult versus infant animals.

Guided bone regeneration is a promising means for reconstructing bone defects in the cranium. The present study was performed to better define those factors that affect osteogenesis in the cranium. The authors studied a single animal model, investigating the contribution of the dura, the pericranium, and the adjacent calvarial bone in the process of calvarial regeneration in both mature and immature animals. Bilateral, 100-mm2, parietal calvariectomies were performed in immature (n = 16) and mature (n = 16) rabbits. Parietal defects were randomized to one of four groups depending on the differential blockade of the dura and/or the pericranium by expanded polytetrafluoroethylene membranes. Animals were humanely killed after 12 weeks, and histometric analysis was performed to quantitate the area of the original bone defect, new bone formation, and new bone density. Bone formation was quantified separately both at the periphery and in the center of the defects. Extrasite bone formation was also quantified both on the dural and on the pericranial sides of the barriers. Bone regeneration was incomplete in all groups over the 12-week study period, indicating that complete bone healing was not observed in any group. The dura was more osteogenic than the pericranium in mature and immature animals, as there was significantly more extrasite bone formed on the dural side in the double expanded polytetrafluoroethylene barrier groups. In both the dural and the double expanded polytetrafluoroethylene barrier groups, dural bone production was significantly greater in immature compared with mature animals. The dura appeared to be the source of central new bone, because dural blockade in the dural and double expanded polytetrafluoroethylene groups resulted in a significant decrease in central bone density in both mature and immature animals. Paradoxically, isolation of the pericranium in mature animals resulted in a significant reduction in total new bone area, whereas pericranial contact appeared to enhance peripheral new bone formation, with the control group having the greatest total new bone area. The present study establishes a model to quantitatively study the process of bone regeneration in calvarial defects and highlights differences in the contribution of the dura and pericranium to calvarial bone regeneration between infant and adult animals. On the basis of these findings, the authors propose that subsequent studies in which permeability of the expanded polytetrafluoroethylene membranes is altered to permit migration of osteoinductive proteins into the defect while blocking prolapse of adjacent soft tissues may help to make guided bone regeneration a realistic alternative for the repair of cranial defects.

Vibration injury damages arterial endothelial cells

Prolonged exposure to hand‐transmitted vibration can cause debilitating neural and vascular dysfunction in humans. It is unclear whether the pathophysiology involves simultaneous or sequential injury of arteries and nerves. The mechanism of vibration injury was investigated in a rat tail model, containing arteries and nerves structurally similar to those in the human hand. Tails were selectively vibrated for 1 or 9 days with the remainder of the animal at rest. One vibration bout of 4 h/day, 60 HZ, 5 g (49 m/s2) acceleration, injured endothelial cells. Injury was signaled by elevated immunostaining for NFATc3 transcription factor. Electron microscopy revealed that vibration for 9 days produced loss and thinning of endothelial cells, with activated platelets coating the exposed subendothelial tissue. Endothelial cells and arterial smooth muscle cells contained double membrane–limited, swollen processes indicative of vasoconstriction‐induced damage. Laser doppler surface recording demonstrated that 5 min of vibration significantly diminished tissue blood perfusion. These findings indicate that early injury involves vasoconstriction and denuding of the arterial endothelium.

A protocol for use of medetomidine anesthesia in rats for extended studies using task-induced BOLD contrast and resting-state functional connectivity

The alpha-2-adrenoreceptor agonist, medetomidine, which exhibits dose-dependent sedative effects and is gaining acceptance in small-animal functional magnetic resonance imaging (fMRI), has been studied. Rats were examined on the bench using the classic tail-pinch method with three infusion sequences: 100 microg/kg/h, 300 microg/kg/h, or 100 microg/kg/h followed by 300 microg/kg/h. Stepping the infusion rate from 100 to 300 microg/kg/h after 2.5 h resulted in a prolonged period of approximately level sedation that cannot be achieved by a constant infusion of either 100 or 300 microg/kg/h. By stepping the infusion dosage, experiments as long as 6 h are possible. Functional MRI experiments were carried out on rats using a frequency dependent electrical stimulation protocol-namely, forepaw stimulation at 3, 5, 7, and 10 Hz. Each rat was studied for a four-hour period, divided into two equal portions. During the first portion, rats were started at a 100 microg/kg/h constant infusion. During the second portion, four secondary levels of infusion were used: 100, 150, 200, and 300 microg/kg/h. The fMRI response to stimulation frequency was used as an indirect measure of modulation of neuronal activity through pharmacological manipulation. The frequency response to stimulus was attenuated at the lower secondary infusion dosages 100 or 150 microg/kg/h but not at the higher secondary infusion dosages 200 or 300 microg/kg/h. Parallel experiments with the animal at rest were carried out using both electroencephalogram (EEG) and functional connectivity MRI (fcMRI) methods with consistent results. In the secondary infusion period using 300 microg/kg/h, resting-state functional connectivity is enhanced.

The nasolabial fold ; an anatomic and histologic reappraisal

The nasolabial fold was analyzed by anatomic and histologic evaluation of the tissue planes that create and surround the fold. A fascial-fatty layer exists in the superficial subdermal space extending from the upper lip across the nasolabial fold to the cheek mass. The SMAS is present in the upper lip as the superficial portion of the orbicularis oris muscle. Traction on the SMAS or periosteum lateral to the nasolabial fold can deepen the fold, while traction on the fascial-fatty layer lessens the fold. The fascial-fatty layer and skin of the cheek mass are suggested as the primary ptotic elements responsible for facial aging. (Plast. Reconstr. Surg. 93: 60, 1994.)

Interhemispheric neuroplasticity following limb deafferentation detected by resting-state functional connectivity magnetic resonance imaging (fcMRI) and functional magnetic resonance imaging (fMRI)

Functional connectivity magnetic resonance imaging (fcMRI) studies in rat brain show brain reorganization following peripheral nerve injury. Subacute neuroplasticity was observed 2 weeks following transection of the four major nerves of the brachial plexus. Direct stimulation of the intact radial nerve reveals a functional magnetic resonance imaging (fMRI) activation pattern in the forelimb regions of the sensory and motor cortices that is significantly different from that observed in normal rats. Results of this fMRI experiment were used to determine seed voxel regions for fcMRI analysis. Intrahemispheric connectivities in the sensorimotor forelimb representations in both hemispheres are largely unaffected by deafferentation, whereas substantial disruption of interhemispheric sensorimotor cortical connectivity occurs. In addition, significant intra- and interhemispheric changes in connectivities of thalamic nuclei were found. These are the central findings of the study. They could not have been obtained from fMRI studies alone-both fMRI and fcMRI are needed. The combination provides a general marker for brain plasticity. The rat visual system was studied in the same animals as a control. No neuroplastic changes in connectivities were found in the primary visual cortex upon forelimb deafferentation. Differences were noted in regions responsible for processing multisensory visual-motor information. This incidental discovery is considered to be significant. It may provide insight into phantom limb epiphenomena.

THE LATERAL ARM FASCIAL FREE FLAP : ITS ANATOMY AND USE IN RECONSTRUCTION

Free fascial transfer has been used for reconstruction of gliding surfaces of the upper and lower extremities or when thin, pliable coverage is required (hand, heel, nose, and ear). In our experience with the lateral arm fasciocutaneous flap, we have found that the fascia alone is an excellent source of tissue for free flap transfer. A thorough investigation of the microscopic, gross, and radiographic anatomy of the lateral arm fascia was undertaken by the study of 25 fresh cadavers. Vascular pathways were mapped, their locations were analyzed, and then they were correlated with the elevation, design, and transfer of the flap. The lateral arm has a large fascial component located anterior and posterior to the lateral intermuscular septum, which itself lies between the triceps and the brachialis and brachioradialis muscles. It is perfused by the posterior radial collateral artery (PRCA), one of the terminal branches of the profunda brachii. This vessel (PRCA) provides at least four fascial branches from 1 to 15 cm proximal to the lateral epicondyle, the largest of which is located an average of 9.7 cm superior to the lateral epicondyle. Fascia up to 12 x 9 cm may be used with good axial perfusion. The histologic cross sections demonstrate the complex anatomy of the fascia itself, as well as its relation to the nutrient vessels. We have applied the lateral arm fascial flap in five cases of upper extremity reconstruction. We have also found this flap valuable in preservation of underlying anatomic detail for total reconstruction of the ear and nose when local tissue and more conventional flaps were not available.

Psychological adjustment following work-related hand injury : 18-month follow-up

Severe, work-related hand injuries are often accompanied by a significant number of psychological symptoms that are frequently associated with posttraumatic stress disorders. These symptoms occur in the following four domains of psychological functioning: cognitive, affective, physiological, and behavioral. This study examined the incidence of a variety of symptoms occurring with work-injured patients. Interviews were conducted at 1 week, 3 months, 6 months, 12 months, and 18 months after injury. Symptom frequencies were recorded. The results indicate that many of these symptoms were persistent 18 months later and continued to be significantly debilitating. The results support the need for psychological intervention after severe, work-related hand injuries.

Glomus tumor imaging: Use of MRI for localization of occult lesions

Magnetic resonance imaging has been performed in six patients with glomus tumors of the hand and correlated with clinical surgical histopathologic findings and with angiography in one case. Two of the patients had obscure pain without the classic clinical and radiologic findings of glomus tumors. The MRI examinations depicted the tumors in excellent detail and facilitated diagnosis in the two patients with atypical presentation. In all six cases the diagnoses were confirmed at surgery. The MRI proved valuable as a noninvasive and accurate means for the early diagnosis of occult glomus tumors.

The nasolabial fold: a photogrammetric analysis.

The nasolabial fold was analyzed by studying changes with aging in the nasolabial fold and adjacent soft-tissue features. Chronologic photographs were obtained from 19 older subjects, taken approximately every 10 years, from age 20 to their present age. In a separate phase of the study, facial portraits in repose and smiling were taken of young and old adult subjects with a mechanical frame used for setting an objective point of reference. Facial landmarks were identified and depth measurements were made in the anteroposterior direction. Relative lengths of selected points also were determined in the other dimensions (in the coronal plane) from photographs; these distances were normalized by using lower face length (distance from medial canthus to menton) for the vertical orientation and interpupillary distance to normalize horizontal dimensions. It was found that with aging there is anterior, lateral, and inferior displacement of the cheek mass with a resultant deepening of the nasolabial fold, while relationships between the upper lip and the fold itself remain constant.Also with age, the lateral commissure was found to move laterally, while the apparent angle of the nasolabial fold was decreased; this latter dimension was reflected by a decrease in the horizontal component of the fold length. These results support the theory that nasolabial fold deepening with age is caused by changes in the cheek mass and its support. (Plast. Reconstr. Surg. 93: 70, 1994.)