Early detection of cerebral glucose uptake changes in the 5XFAD mouse.

Brain glucose hypometabolism has been observed in Alzheimer's disease (AD) patients, and is detected with (18)F radiolabelled glucose, using positron emission tomography. A pathological hallmark of AD is deposition of brain ß- amyloid plaques that may influence cerebral glucose metabolism. The five times familial AD (5XFAD) mouse is a model of brain amyloidosis exhibiting AD-like phenotypes. This study examines brain ß-amyloid plaque deposition and (18)FDG uptake, to search for an early biomarker distinguishing 5XFAD from wild-type mice. Thus, brain (18)FDG uptake and plaque deposition was studied in these mice at age 2, 5 and 13 months. The 5XFAD mice demonstrated significantly reduced brain (18)FDG uptake at 13 months relative to wild-type controls but not in younger mice, despite substantial ß- amyloid plaque deposition. However, by comparing the ratio of uptake values for glucose in different regions in the same brain, 5XFAD mice could be distinguished from controls at age 2 months. This method of measuring altered glucose metabolism may represent an early biomarker for the progression of amyloid deposition in the brain. We conclude that brain (18)FDG uptake can be a sensitive biomarker for early detection of abnormal metabolism in the 5XFAD mouse when alternative relative uptake values are utilized.

Compressed sensing reconstruction improves sensitivity of variable density spiral fMRI.

PURPOSE: Functional MRI (fMRI) techniques that can provide excellent blood oxygen level dependent contrast, rapid whole brain imaging, and minimal spatial distortion are in demand. This study explored whether fMRI sensitivity can be improved through the use of compressed sensing (CS) reconstruction of variable density spiral fMRI. METHODS: Three different CS-reconstructed 1-shot variable density spirals were explored (corresponding to 28%, 35%, and 46% under-sampling), and compared with conventional 1-shot and 2-shot Archimedean spirals acquired using matched echo time and volume repetition time. fMRI maps were reconstructed with or without CS MRI and sensitivity was compared using identically matched voxels. RESULTS: The results demonstrated that an l1 -norm based CS reconstruction only led to an increase in functional contrast when applied to 28% under-sampled data. A whole brain t-contrast map revealed that 2-shot uniformly sampled spiral and 28% under-sampled spiral data reconstructed with CS yield equivalent sensitivity, even with matched echo time and volume repetition time CONCLUSION: VD spiral exhibits a useful operating range, in the region of 25-30% under-sampling, for which CS reconstruction can be used to increase the sensitivity of fMRI to brain activity. Using CS, VD acquisitions achieve the same sensitivity as 2-shot Archimedean acquisitions, but require only a single shot.

Degradation and drug release in calcium polyphosphate bioceramics: an MRI-based characterization.

Degradable, bioceramic bone implants made of calcium polyphosphate (CPP) hold potential for controlled release of therapeutic agents in the treatment of localized bone disease. Magnetic resonance imaging techniques for non-invasively mapping fluid distribution, T(1) and T(2) relaxation times and the apparent diffusion coefficient were performed in conjunction with a drug elution protocol to resolve free and bound water components within the material microstructure in two CPP formulations (G1 and G2). The T(2) maps provided the most accurate estimates of free and bound water, and showed that G1 disks contained a detectable free water component at all times, with drug release dominated by a Fickian diffusion mechanism. Drug release from G2 disks was characterized by a combined diffusional/structural relaxation mechanism, which may be related to the gradual infiltration of a free water component associated with swelling and/or chemical degradation.

Validity of health status measures in patients with ulnar wrist disorders.

PURPOSE: To assess measurement properties and construct validity of health status measures. METHOD: Forty-three patients with surgically managed ulnocarpal impingement completed a self-report mail survey, including regional (Disabilities of the Arm, Shoulder and Hand [DASH] questionnaire), disease-specific (Brigham Functional Scale), and generic (Short Form 36 [SF-36] Acute Health Survey) health status measures and questions on condition severity and work status. STATISTICAL ANALYSIS: Scores were transformed and frequency distributions constructed to compare the distribution of responses to the measures. Correlation analysis and analysis of variance were applied to assess construct validity. RESULTS: The DASH and Brigham questionnaires had similar distributions of scores, with a slightly greater spread of responses and no ceiling effect on the DASH. Patients appeared slightly less healthy on the basis of the SF-36 scores, which reflected in part the effect of comorbidities. Both the DASH and the Brigham discriminated across levels of severity and work status; the DASH also discriminated on the basis of type of surgery. The SF-36 was able to discriminate some constructs but not as well as the regional and disease-specific measures. CONCLUSION: This study provides evidence of construct validity for the DASH and Brigham questionnaires in patients with ulnar wrist problems in the late post-operative period.

Health status following recessional ulnar osteotomy.

This study describes the health status of 31 patients who underwent recessional ulnar osteotomy for ulnocarpal impingement. An additional lunotriquetral fusion was performed in 11/31 patients for joint degeneration. Outcomes included the DASH (Disability of arm, shoulder and hand) questionnaire, SF-36 Acute Health Survey, complications, and satisfaction with surgical outcome. Patients were stratified into two groups for analysis: osteotomy alone and osteotomy + fusion. The overall results indicated that osteotomy plus fusion in patients with more advanced ulnocarpal impingement did not equalise patients' post-operative health status to that reported by patients requiring osteotomy alone. Mean DASH and SF-36 physical component scores indicated better health status in the osteotomy group compared with the osteotomy + fusion group after surgery. Forty-one point nine per cent of patients required plate removal, and scar pain persisted in 58%. One patient in each group developed a non-union requiring revision surgery. Patients in both groups were generally satisfied with their surgical result, with a higher proportion of very or completely satisfied patients in the osteotomy group (65%) compared to the osteotomy + fusion group (27%). Overall, recessional ulnar osteotomy appears to be a successful procedure for the treatment of ulnocarpal impingement.

Epiphyseal plate transplantation between sites of different growth potential.

The purpose was to study epiphyseal plate growth after microvascular transplantation to sites of different growth potential. The hypothesis was that the growth potential of an epiphyseal plate transplant is a function of the donor irrespective of the recipient site to which it is transplanted. Immature rabbits were used in an experiment that transplanted microsurgically revascularized second metatarsal epiphyseal plates. There were three experimental groups in which transplants were made to (i) sites of the same growth potential (orthotopic), (ii) sites of higher growth potential (proximal tibia), and (iii) sites of lower growth potential (third metacarpal). Control groups were nonoperated animals, animals with an anteromedial proximal tibial osteotomy, and nonoperated contralateral limbs of all experimental animals. Postoperative graft viability was checked with fluorochrome labeling. Postoperative growth was measured from serial standardized radiographs. Follow-up was for either 5 or 8 weeks. Animals were then killed, and epiphyseal plate specimens removed for histomorphometric analysis. Results showed that the total growth of experimental second metatarsal transplants was not statistically different (p > 0.05) in any recipient site. It was noted, however, that transplanted epiphyseal plates in all experimental groups grew at lower rates than nonoperated controls.

In vivo measurements of multi-component T2 relaxation behaviour in guinea pig brain.

Multi-echo Carr-Purcell-Meiboom-Gill (CPMG) imaging sequences were implemented on 1.5 T and 4.0 T imaging systems to test their ability to measure in vivo multi-component T2 relaxation behavior in normal guinea pig brain. The known dependence of accurate T2 measurements on the signal-to-noise ratio (SNR) was explored in vivo by comparing T2 decay data obtained using three methods to increase SNR (improved RF coil design, signal averaging and increased magnetic field strength). Good agreement between T2 values of nickel-doped agarose phantoms was found between imaging and spectroscopic methods. T2 values were determined for gray matter (GM) and white matter (WM) locations from images of guinea pig brain in vivo. T2 measurements of GM were found to be monoexponential at both field strengths. The mean T2 times for GM were 71 ms at 1.5 T, and 53 ms at 4.0T. The highest average SNR was achieved using an improved RF coil at 4.0T. In this case, two peaks were extracted in WM, a "short" T2 peak at approximately 6 ms, and a "medium" T2 peak at approximately 48 ms. T2 values in GM and the major component of WM were significantly decreased at 4.0T compared to 1.5 T. The improved SNR attained with this optimized imaging protocol at 4.0T has allowed for the first time extraction of the myelin-sensitive T2 component of WM in animal brain in vivo.

Transplantation of epiphyseal plate allografts between animals of different ages.

The purpose of the experiment was to study growth of epiphyseal plate allografts after transplantation into subjects of a different age, thus preparing for future transplantation of epiphyseal plate or extremity allografts in children. Microvascular transplantation of proximal tibial epiphyseal plate allografts was performed in skeletally immature New Zealand White female rabbits. The growth of 9-week-old epiphyseal plate allografts was examined in both 9-week-old and 17-week-old recipients, as was the growth of 17-week-old epiphyseal plate allografts in 17-week-old recipients. Immunosuppression was with cyclosporine (Cyclosporine A). Successful transplants were confirmed with 99mTc-MDP isotope scanning, and growth was evaluated with weekly standardized radiographs until death. Growth rate was found to depend on the age of the donor epiphyseal plate and was independent of the age of the recipient. This has clinical implications for the procurement of donor tissue in potential transplantation of epiphyseal plate allografts in children.

Unsatisfactory outcome after lower limb salvage: decision-making pitfalls.

We examined unsatisfactory outcome after microvascular reconstruction of 34 injured lower extremities at the Toronto Hospital between 1987 and 1992. Our purpose was to examine those factors that contributed to poor outcome in order to improve decislon making when treating the traumatized lower extremity. For the purpose of this review, poor outcome was defined by either secondary elective amputation or patient dissatisfaction. Patients were divided according to preoperative problem into one of three groups: osteo/cutaneous deficit (group 1), septic nonunion (group 2), and osteomyelitis (group 3). Despite successful microvascular reconstruction in each case, unsatisfactory outcome occurred in six (18%) patients. Four had undergone secondary elective amputation, and two were dissatisfied because of residual pain from another musculoskeletal source. Close examination of the factors that contributed to poor outcome in each of these cases has allowed identification of potential pitfalls that may compromise final outcome after limb salvage. On the basis of our observations and an up-to-date review of the relevant literature, we provide basic guidelines as to when and when not to attempt limb salvage.

An ultrastructural study of the intimal hyperplasia in healing microarterial anastomoses.

The purpose of the study was to investigate the ultrastructure of intimal hyperplastic cells. End-to-end microarterial anastomoses were studied in a rabbit free-tissue-transfer model. There were five experimental groups, with 1, 3, 7, 14, or 28 days follow-up. At sacrifice the anastomoses were tested for patency and then examined by light and electron microscopy. At days 1 and 3 the repaired intima was covered with macrophages and extravasated erythrocytes. At day 7 spindle-shaped fibroblasts with copious rough endoplasmic reticulum were seen. Some of these cells also contained pinocytotic vesicles, filaments with focal densities, and subplasmalemmal attachment sites, the features of smooth muscle cells. At day 14, more cells contained smooth muscle features and these features were also more pronounced. These young myofibroblasts were plumper than adjacent fibroblasts. At day 28 mature myofibroblasts with a full complement of organelles were present. The results, therefore, supported the hypothesis that myofibroblasts are present in the intimal hyperplasia of healing microarterial anastomoses.

Limb salvage surgery and adjuvant radiotherapy for soft tissue sarcomas of the forearm and hand.

Twenty-five consecutive patients with soft tissue sarcoma of the forearm and hand were assessed for limb-salvage surgery and were entered into a prospective study evaluating oncologic details and functional outcome. Seventeen patients had received incomplete primary excision elsewhere and presented with local recurrence or residual disease. Three had pulmonary metastases at the time of presentation. Twenty-three patients were candidates for limb-salvage surgery and 20 received adjuvant radiotherapy. The mean follow-up period was 37 months. There was local recurrence in three patients who had initially received marginal excision of the primary sarcoma, and three patients died of systemic disease. Limb function was assessed prospectively using both patient-based and clinician-based functional scoring systems and revealed good to excellent results in all but three patients. Eighty-eight percent of those who survived and did not require amputation were able to return to occupational and activities of daily living with no or minimal functional limitation. This study demonstrates that limb-salvage surgery, with adjuvant radiotherapy when necessary, is an effective alternative to amputation in the majority of patients with sarcoma of the forearm and hand. Radiation toxicity is rarely a problem.

Complex injuries of the forearm. Coverage considerations.

Complex forearm injuries involve damage to the skin and underlying tissues. The best results are obtained when a multidisciplinary approach is taken to their management. Management of the acute injury should be done in a manner that takes into consideration late reconstructive procedures and best possible final function outcome. This article reviews initial management and options for soft-tissue coverage. Advantages and disadvantages of a wide variety of procedures are discussed and in addition the authors review some of the more controversial areas and give personal preferences.

Differences in perceived shape from shading correlate with activity in early visual areas.

The perception of shape from shading depends on the orientation of the shading gradient [1] [2] [3] [4]. Displays composed of elements with vertically oriented shading gradients of opposite polarity produce a strong and stable percept of 'concave' and 'convex' elements. If the shading gradients are rotated 90 degrees , the depth percept is reduced and appears much more ambiguous. Results from psychophysical [1] [2] [3] [4] [5] [6], neuropsychological [7] and computational studies [8] [9] suggest that the perception of shape from shading engages specific mechanisms in early cortical visual areas. In a three-dimensional functional magnetic resonance imaging (fMRI) study at 1.5 Tesla using a three-dimensional, interleaved-echoplanar imaging technique and a surface radio frequency (RF) coil placed under the visual cortex, we investigated the activity in these early visual areas associated with viewing shape from shading displays at two different orientations. We found significantly greater activation in area V1 and neighbouring low-level visual areas of cortex when subjects viewed displays that led to weak and unstable depth percepts than when they viewed displays that led to strong and stable depth percepts.

Microsurgical treatment of septic nonunion of the tibia. Quality of life results.

The outcome of microsurgical reconstruction of septic nonunion of the tibia was described. The series consisted of 15 patients, with Cierny Stage IVA or IVB septic nonunion of the tibia, who were treated in the microsurgical practice of a major tertiary care hospital. Patients with a documented end point of either union or amputation were eligible for inclusion. Patients were treated with wound excision followed by soft tissue and skeletal reconstruction. The outcome measures of interest included clinical measures (time to union or amputation, surgical complications, wound status) and health related quality of life measures (Short Form-36, Western Ontario and McMaster Universities Osteoarthritis Index, and patient satisfaction questionnaires). The average followup time was 3 years. There was 1 microvascular complication and no failures. Two of 15 patients (both Cierny IVB) required amputation after reconstruction. The time to union after bone grafting was an average of 6.5 months in May et al Type III legs (n = 12), 3 months in May et al Type IV legs (n = 1), and 16 months in May et al Type V legs (n = 2). Nine patients completed the questionnaires; Short Form-36 scores were below normative values for the same age group. Scores on the activity limitation component of the Western Ontario and McMaster Universities Osteoarthritis Index seem to be comparable with those of individual's scores after total knee replacement surgery. Despite relatively low scores on the questionnaires, most patients were either very or completely satisfied with the outcome of surgery. Patients often reported that satisfaction was related to preservation of the limb.

Lower extremity free flaps: a review.

OBJECTIVE: To identify factors related to free-flap coverage of lower extremity fractures that are linked to a negative outcome. DESIGN: A chart review. SETTING: A large microsurgical referral centre. PATIENTS: From 1981 to 1989, the records of all patients who underwent free-tissue transfer to the lower extremity with more than 1 year of follow-up were selected. From this was drawn a subgroup of 49 patients (mean age, 36 years) who had tibial fractures (55% were motor vehicle injuries) and in almost all cases established soft-tissue or bony defects. They formed the study group. INTERVENTION: Free-flap transfer. OUTCOME MEASURES: Factors that might be associated with free-flap failure: mechanism of injury, grade of tibial fracture, history of smoking, diabetes, peripheral vascular disease, ischemic heart disease, vascular compromise in the leg preoperatively, recipient artery used, type of anastomosis, and hypertension or hypotension intraoperatively. RESULTS: Type IIIB tibial fractures were the most frequent (67%) and carried a significantly (p = 0.02) higher risk of free-flap failure than other types of fracture. Patients underwent a mean of four procedures before referral for free-tissue transfer. The mean time from injury to flap coverage was 1006 days. Stable, long-term coverage of the free flaps was achieved in 78% of patients. Wound breakdown was most often caused by recurrent osteomyelitis (65%). Seventy-four percent of the fractures healed. The amputation rate was 10%. Four patients required repeat free-flap transfer for limb salvage. CONCLUSIONS: Only the grade of tibial fracture could be significantly related to postoperative free-flap failure.

Microvascular anastomoses. A comparative study of fibrinogen adhesive and interrupted suture techniques.

A modified sleeve technique was developed for making microsurgical anastomoses using a commercially produced fibrinogen adhesive called Tisseel. A controlled study was then carried out to compare the new fibrinogen adhesive anastomoses with conventional suture anastomoses in a bilateral groin flap model using 50 consecutive rabbits. Statistical analysis of the results indicated that flap survival rate and vascular patency rate were comparable for the two techniques. The fibrinogen adhesive anastomoses took less time to complete and, subjectively, were less difficult technically. The suture anastomoses were more versatile. Histologic studies revealed that the adhesive did not flow through the sleeve into the lumen, and that, although there was a brief inflammatory response associated with healing, this inflammation was very localized and did not involve the inner layers of the vessel wall or lumen. It was concluded that the new technique was a useful addition to techniques already available.

Microvascular transplantation of physeal allografts.

We compared growth in vascularised allograft transplants, autografts and in non-operated physes in rabbits immunosuppressed with cyclosporin A and in non-immunosuppressed animals. Molecular haplotyping was undertaken before operation to ensure allogenicity. Postoperative bone scans and fluorochrome labelling were used to confirm physeal vascularity. The animals were killed at three or five weeks. Proximal tibial physeal autografts, with or without cyclosporin A, or allografts with cyclosporin A, grew at similar rates to the physes of non-operated rabbits. All the operated physes grew at rates significantly greater than their contralateral controls. 99mTc-MDP bone scans accurately predicted the viability of the epiphyseal plate. Quantitative histomorphological analysis of the heights of the physeal proliferative and hypertrophic zones showed that successful physeal transplants have a normal appearance, but when unsuccessful have thickened hypertrophic zones compatible with physeal ischaemia. We discuss the significance of these results in relation to the transplantation of physes in children.

Restriction fragment-length polymorphism analysis of the major histocompatibility complex in New Zealand white rabbits.

As a model system, rabbits are particularly useful in transplantation studies because of their size and accessibility. However, inbred rabbits of known MHC haplotype are not commercially available, and there are few monoclonal antibody reagents available to permit serological typing of experimental animals prior to transplant. Here we present a rapid and reliable method to distinguish rabbits that differ at their MHC class I and class II loci, and present 34 class I and 16 class II haplotypes determined by restriction fragment-length polymorphism analysis of outbred heterozygous rabbits. The applicability of this molecular typing system to transplantation experiments in the New Zealand White rabbit is discussed.

Can quantitative 99mTc-MDP bone scans be used to predict longitudinal growth of epiphyseal plate allografts after microvascular transplantation? An experimental study.

Allograft and autograft microvascular proximal tibial epiphyseal plate transplants were performed in female New Zealand White (NZW) rabbits to quantify the growth rate and total growth potential of immunosuppressed and nonimmunosuppressed rabbits. The purpose of this experiment is to examine whether the 99mTc-MDP radionuclide uptake of the transplanted epiphyseal plate at 1 week postoperatively, done to assess anastomotic patency of the transplant, could also serve as a predictor of eventual longitudinal growth of the transplant or replant. All transplants and replants demonstrating positive 99mTc-MDP uptake in the proximal tibial epiphyseal plate at 1 week showed continued longitudinal growth. The precise amount of 99mTc-MDP uptake, however, did not correlate with the amount of growth at 3 and 5 weeks follow-up.

Heterotopic microvascular epiphyseal plate transplantation: a new model using the rabbit metatarsal.

The purpose of this study is to develop a new vascularized epiphyseal plate model in the New Zealand White rabbit using a metatarsal epiphyseal plate having limited longitudinal growth potential. Such a model could be utilized in various experiments aimed at manipulating epiphyseal plate growth. The viability of the harvested live subject grafts was demonstrated with continued epiphyseal uptake during Tc99-MDP radionuclide bone scanning. The currently described models used in epiphyseal transplant research all involve long bone epiphyseal plates with significantly greater growth potential than the new metatarsal model. This new model therefore fills a void in the field by allowing investigators to transplant a growth plate with limited growth potential into any heterotopic site and study the effects of various hormonal and physical influences upon epiphyseal plate growth performance.