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Biomedical subjects

G A Becker

Publications and source records attributed to G A Becker.

At least 19 recordsLinked to original sources

Non-invasive assessment of distribution volume ratios and binding potential: tissue heterogeneity and interindividually averaged time-activity curves.

Due to the stochastic nature of radioactive decay, any measurement of radioactivity concentration requires spatial averaging. In pharmacokinetic analysis of time-activity curves (TAC), such averaging over heterogeneous tissues may introduce a systematic error (heterogeneity error) but may also improve the accuracy and precision of parameter estimation. In addition to spatial averaging (inevitable due to limited scanner resolution and intended in ROI analysis), interindividual averaging may theoretically be beneficial, too. The aim of this study was to investigate the effect of such averaging on the binding potential ( BP) calculated with Logan's non-invasive graphical analysis and the "simplified reference tissue method" (SRTM) proposed by Lammertsma and Hume, on the basis of simulated and measured positron emission tomography data [[(11)C] d- threo-methylphenidate (dMP) and [(11)C]raclopride (RAC) PET]. dMP was not quantified with SRTM since the low k(2) (washout rate constant from the first tissue compartment) introduced a high noise sensitivity. Even for considerably different shapes of TAC (dMP PET in parkinsonian patients and healthy controls, [(11)C]raclopride in patients with and without haloperidol medication) and a high variance in the rate constants (e.g. simulated standard deviation of K(1)=25%), the BP obtained from average TAC was close to the mean BP (error <5%). However, unfavourably distributed parameters, especially a correlated large variance in two or more parameters, may lead to larger errors. In Monte Carlo simulations, interindividual averaging before quantification reduced the variance from the SRTM (beyond a critical signal to noise ratio) and the bias in Logan's method. Interindividual averaging may further increase accuracy when there is an error term in the reference tissue assumption E= DV(2)- DV' ( DV(2) = distribution volume of the first tissue compartment, DV' = distribution volume of the reference tissue). This can be explained by the fact that the distribution volume ratio ( DVR= DV/DV') obtained from averaged TAC is an approximation for Sigma DV/Sigma DV' rather than for Sigma DVR/ n. We conclude that Logan's non-invasive method and SRTM are suitable for heterogeneous tissues and that discussion of group differences in PET studies generally should include qualitative and quantitative assessment of interindividually averaged TAC.

Computer Simulation↗

Assessment of porcine bone metabolism by dynamic.

UNLABELLED: The aim of this study was to quantify regional bone blood flow and [(18)F]fluoride ion influx with [(18)F]fluoride ion PET and correlate the results with specific static and dynamic indices of bone metabolism in healthy pigs. METHODS: During continuous ventilation (fractional concentration of oxygen in inspired gas = 0.3), dynamic PET scans 120 min in duration were obtained for 9 mini pigs after intravenous injection of 10.0 +/- 1.2 MBq (mean +/- SD) of [(18)F]fluoride ion per kilogram of body weight. Iliac crest bone biopsies were performed immediately before the PET scan to determine static and dynamic indices of bone metabolism (i.e., the mineral apposition rate) by bone histomorphometry. Kinetic rate constants describing influx (K(1)) and efflux (k(2)) of [(18)F]fluoride as well as chemisorption and incorporation of [(18)F]fluoride (k(3)) and reverse transport (k(4)) were determined for 6 vertebral bodies in each animal. Blood flow estimates (f) were derived from K(1) values corrected for the permeability-surface area product using a previously derived correction algorithm. A rate constant describing the net forward transport rate of fluoride (K(i)) and the fluoride volume flux (K(flux)) derived from a 2-tissue-compartment model was calculated and compared with the results of Patlak graphic analysis (K(pat)). RESULTS: A significant correlation was found between mineral apposition rate and K(i) (P < 0.005), K(flux) (P < 0.01), K(pat), K(1), and f (P < 0.05). The values of f, K(i), K(flux), and K(pat) did not correlate significantly with other static or dynamic histomorphometric indices or with age, serum alkaline phosphatase, or parathyroid hormone levels. The values of f and K(i) correlated linearly (y = 0.023 + 0.32x; r(2) = 0.74; P < 0.001). CONCLUSION: PET bone studies using [(18)F]fluoride ion provide quantitative estimates of bone blood flow and metabolic activity that correlate with histomorphometric indices of bone formation in the normal bone tissue of the mini pig. Therefore, it seem reasonable to assume that [(18)F]fluoride ion PET can reduce the number of invasive bone biopsies, thus facilitating follow-up of patients with metabolic bone diseases.

Animals↗

Allogenic bone graft viability after hip revision arthroplasty assessed by dynamic [18F]fluoride ion positron emission tomography.

The biological fate of allogenic bone grafts in the acetabular cavity and their metabolic activity after acetabular augmentation is uncertain but is most important for the stability of hip implants after hip revision arthroplasty. The aim of this study was to quantify regional bone metabolism after hip replacement operations. Dynamic [18F]fluoride ion positron emission tomography (PET) was used to investigate the metabolic activity of acetabular allogenic bone grafts and genuine bone, either 3-6 weeks (short-term group, n = 9) or 5 months to 9 years (long-term group, n = 10) after hip revision arthroplasty. Applying a three-compartment model, the fluoride influx constant was calculated from individually fitted rate constants (Knlf) and by Patlak graphical analysis (Kpat). The results were compared with genuine cancellous and cortical acetabular bone of contralateral hips without surgical trauma (n = 7). In genuine cortical bone, Knlf was significantly increased in short- (+140.9%) and long-term (+100.0%) groups compared with contralateral hips. Allogenic bone grafts were characterised by a significantly increased Knlf in the short-term group (+190.9%) compared with contralateral hips, but decreased almost to the baseline levels of contralateral hips (+45.5%) in the long-term. Values of Knlf cor-related with the rate constant K1 in genuine (r = 0.89, P<0.001) and allogenic bone regions (r = 0.79, P<0.001), indicating a coupling between bone blood flow and bone metabolism in genuine bone as well as allogenic bone grafts. Kpat values were highly correlated with Knlf measurements in all regions. In conclusion, [18F]fluoride ion PET revealed the presence of an increased host bone formation in allogenic bone grafts early after hip revision arthroplasty. In contrast to genuine cortical bone, allogenic bone graft metabolism decreased over time, possibly due to a reduced ability to respond to the same extent as genuine bone to elevated metabolic demands after surgery.

Aged↗

Blood flow measurements with [(15)O]H2O and [18F]fluoride ion PET in porcine vertebrae.

A dual positron emission tomography (PET) tracer study with [18F]fluoride and the freely diffusible tracer [(15)O]H2O was performed to measure the capillary transport of [18F]fluoride and to evaluate the potential of [18F]fluoride ion PET to quantitate bone blood flow. Under the condition of a high predictable single-pass extraction fraction (E(F)) for [18F]fluoride, the [18F]fluoride ion influx transport constant (K1F), derived from kinetic [18F]fluoride ion PET measurements, can be used to estimate bone blood flow. Bone blood flow was measured in vertebral bodies by dynamic [(15)O]H2O PET during continuous ventilation with N2O, O2, and Isoflurane (FiO2 = 0.3) in seven adult mini pigs, followed by dynamic [18F]fluoride ion PET. The mean blood flow measured by [(15)O]H2O (FlowH2O) was 0.145 +/- 0.047 ml x minute(-1) x ml(-1) and the mean K1F was 0.118 +/- 0.031 ml x minute(-1) x ml(-1), respectively (mean +/- SD). Regional analysis showed excellent agreement between FlowH2O and K1F at low flow and a significant underestimation of flow by K1F relative to FlowH2O in regions of normal and elevated flow. The observed relationship between parameters followed the Renkin-Crone distribution. The permeability-surface product was determined as 0.25 minute(-1) for vertebral bodies consisting of a mixture of trabecular and cortical bone. We conclude that [18F]fluoride ion PET can be used to estimate bone blood flow in low and normal flow regions, as long as the flow dependency of the E(F) is taken into consideration. Above blood flow values of 0.2 to 0.35 ml x minute(-1) x ml(-1), the magnitude of K1F is increasingly independent on blood flow because diffusion limits tracer transport.

Animals↗

A treatment approach for isolated unicondylar fractures of the proximal phalanx.

We developed a protocol to improve the final total active motion for patients with isolated unicondylar fractures of the head of the proximal phalanx. The protocol includes surgical treatment followed by hand therapy. Surgical fixation is obtained using lag screw technique. Therapy includes immediate mobilization by use of a continuous passive motion machine and controlled active motion. Specially designed splints and Coban wrap are used to control the position of the digit during the first six months following surgery. Silastic gel is used to control scarring. We treated five consecutive patients over a 4-year period using this protocol. Final total active motion of the injured digit averaged 241 degrees--approximately 90% of the normal range of 260 to 270 degrees. No patients required secondary surgery.

Adolescent↗

Immune pancytopenia.

Circulating T-lymphocytes from a 13-year-old boy with autoimmune anaemia, severe neutropenia and thrombocytopenia inhibited autologous and normal homologous bone marrow myeloid colony formation in vitro. This inhibition was abolished when the patient's antithymocyte globulin and complement-treated T-lymphocytes were used. T-lymphocytes from normal individuals did not cause such an inhibition. The patient's lymphocytes showed no inhibitory effect on erythroid colony formation. Investigation of the patient's serum failed to disclose any leucoagglutinin, lymphocytotoxin or humoral factor against myeloid colony formation. These findings indicate that T-lymphocytes may play a role in the pathogenesis of neutropenia in immune pancytopenia.

Adolescent↗

Prostaglandin E 1 in preparation and storage of platelet concentrates.

The addition of prostaglandin E(1) to blood collection bags improved platelet harvesting; platelets were, esily suspended immediately after centrifugation. The treatment with prostaglandin E(1) did not affect the survival time of these platelets after infusion into a recipient.

Autoradiography↗