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Biomedical subjects

T J Farrell

Publications and source records attributed to T J Farrell.

18 recordsLinked to original sources

Quantification of bioluminescence images of point source objects using diffusion theory models.

A simple approach for estimating the location and power of a bioluminescent point source inside tissue is reported. The strategy consists of using a diffuse reflectance image at the emission wavelength to determine the optical properties of the tissue. Following this, bioluminescence images are modelled using a single point source and the optical properties from the reflectance image, and the depth and power are iteratively adjusted to find the best agreement with the experimental image. The forward models for light propagation are based on the diffusion approximation, with appropriate boundary conditions. The method was tested using Monte Carlo simulations, Intralipid tissue-simulating phantoms and ex vivo chicken muscle. Monte Carlo data showed that depth could be recovered within 6% for depth 4-12 mm, and the corresponding relative source power within 12%. In Intralipid, the depth could be estimated within 8% for depth 4-12 mm, and the relative source power, within 20%. For ex vivo tissue samples, source depths of 4.5 and 10 mm and their relative powers were correctly identified.

Algorithms↗

A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations.

A photon diffusion model has been developed to calculate the steady-state spatially resolved fluorescence from pencil beam excitation in layered tissue. The model allows the calculation of both the excitation reflectance and the fluorescence escape for an arbitrary continuous depth distribution of tissue optical properties and fluorophore concentration. The validity of this model was verified by comparison with Monte Carlo simulations and experimental measurements using phantoms with tissue-like optical properties. The potential usefulness of the spatially resolved fluorescence was explored using the model and simulations of realistic drug distributions. It was shown that using this technique it may be possible to quantify the diffusion of a topically administered drug into the skin, or the photobleaching of a sensitizer during photodynamic therapy.

Algorithms↗

Experimental verification of the effect of refractive index mismatch on the light fluence in a turbid medium.

Diffusion theory is often used to model the transport of light within tissue. It can be used to calculate the light fluence rate in tissue, for example, during photodynamic therapy, or to measure the absorption and scattering properties of tissue. For both of these applications, the influence of the interface between the tissue and the exterior medium on the fluence rate inside the tissue must be known in order to make accurate calculations. We present an experimental investigation of the effect of the refractive index mismatch at the tissue interface on the internal light fluence rate and on the spatially resolved diffuse reflectance as the boundary conditions of the tissue/external medium are changed. The effects of changing the relative refractive index at the boundary are compared to predictions of diffusion theory. The effect of the refractive index mismatch is predicted correctly by diffusion theory.

Animals↗

Anisotropy of light propagation in human skin.

Using spatially resolved, steady state diffuse reflectometry, a directional dependence was found in the propagation of visible and near infrared light through human skin in vivo. The skin's reduced scattering coefficient mu(s)' varies by up to a factor of two between different directions of propagation at the same position. This anisotropy is believed to be caused by the preferential orientation of collagen fibres in the dermis, as described by Langer's skin tension lines. Monte Carlo simulations that examine the effect of partial collagen fibre orientation support this hypothesis. The observation has consequences for non-invasive diagnostic methods relying on skin optical properties, and it could be used non-invasively to determine the direction of lines of cleavage in order to minimize scars due to surgical incisions.

Algorithms↗

Beta2-microglobulin in hypertensive pregnancies.

Beta2-Microglobulin (beta2-m) is a polypeptide that is freely filtered and then mostly reabsorbed and degraded in the proximal renal tubule. Beta2-m is a marker of glomerular filtration (GFR) in renal failure, whereas urinary beta2-m is a marker of proximal renal tubular dysfunction. Preeclampsia (PE) (ie, de novo hypertension in pregnancy with accompanying renal, cerebral, or liver disease or thrombocytopenia) often has renal involvement characterized by proteinuria, decreasing glomerular filtration, or renal tubular dysfunction. The aim of this study was to determine whether serum beta2-m concentration or urinary beta2-m excretion were greater in women with PE than in women with gestational hypertension (GH) (ie, isolated de novo hypertension in the second half of pregnancy) and normal pregnant women. Seventy-five pregnant women (35 with PE, 22 with GH, and 18 normotensives) were studied prospectively. Serum creatinine and beta2-m concentrations, 24-hour proteinuria, and fractional excretion (FE) of beta2-m were measured. Preeclamptics had similar serum creatinine but higher serum beta2-m (3.26+/-0.99 mg/L) than gestational hypertensives (2.44+/-0.77 mg/L; P = 0.016), and both groups had higher serum beta2-m than controls (1.62+/-0.54 mg/L; P = 0.001). FE of beta2-m was similar amongst groups (PE: 0.27%; interquartile range [IQR]: 0.20-0.86; GH: 0.21%; IQR: 0.11-0.40; controls: 0.26%, IQR: 0.12-0.69). PE is characterized by higher serum beta2-m but similar serum creatinine to GH. Because FE beta2-m is similar in these groups, this implies reduced filtering of beta2-m in PE rather than altered tubular handling of beta2-m. Further studies are now necessary to assess whether measurement of serum beta2-m is helpful in the clinical management of the hypertensive disorders of pregnancy.

Creatinine↗

Comparison of the in vivo photodynamic threshold dose for photofrin, mono- and tetrasulfonated aluminum phthalocyanine using a rat liver model.

The photodynamic threshold dose in normal rat liver was determined from the measured depth of necrosis following surface irradiation. The threshold was determined for the photosensitizing drugs Photofrin and monosulfonated aluminum chlorophthalocyanine, AlPcS1, at 24 h postinjection and was found to be (3.4 x/divided by 1.3) x 10(18) and (8.2 x/divided by 1.5) x 10(18) photons cm-3, respectively, compared with the previously reported value of (38 +/- 2) x 10(18) photons cm-3 for the tri/tetrasulfonated phthalocyanine, AlPcS4. These values were independent of drug concentration or total light fluence. For all three drugs the depth of tissue necrosis decreased as the time between drug and light administration increased from 10 min to 72 h. This decrease can be attributed both to the change in the tissue drug concentration as well as to changes in the efficiency of photodynamic therapy for producing tissue damage, related to the photodynamic necrosis threshold. The threshold values for all three photosensitizers were lowest at 10 min post injection: (1.4 x/divided by 1.4) x 10(18), (1.6 x/divided by 1.3) x 10(18) and (23 x/divided by 1.3) x 10(18) photons cm-3 for Photofrin, AlPcS1 and AlPcS4, respectively. The changes in necrosis threshold with time may be due to an initial change from entirely vascular to a combination of vascular and cellular damage, with later redistribution of the photosensitizer to targets at the subcellular level.

Animals↗

The expression of acylphosphatase is associated with the metastatic phenotype in human colorectal tumors.

We have performed differential display comparing gene expression from cell lines derived from human colorectal tumors. The cell lines were selected for study based on their ability to form metastases following injection into athymic mice. One gene which was expressed exclusively by the metastatic lines was identified as human acylphosphatase (e.c. 3.6.1.7, acylphosphate phosphohydrolase). The expression of this gene was confirmed by RT-PCR using gene-specific primers. This gene product catalyzes the hydrolysis of phosphorylated intermediates of Na+/K(+)-ATPase and of Ca(2+)-ATPases of mammalian cells. Changes in the activity of the Na+/K(+)-ATPase pump, regulated by acylphosphatase, have been previously reported in chemically-induced colonic tumors. The differential expression of this gene in the human metastatic colorectal lines suggests it may be involved in the metastatic phenotype.

Acid Anhydride Hydrolases↗

Pancreatic resection combined with intraoperative radiation therapy for pancreatic cancer.

OBJECTIVE: The objective of the study was to analyze a single center's experience in the treatment of pancreatic carcinoma with a combination of pancreatic resection and intraoperative radiation therapy (IORT). SUMMARY BACKGROUND DATA: Pancreatic cancer is the most lethal form of gastrointestinal malignancy. Historically, it carries a 20% 1-year survival and a 5-year survival of 3% to 5%. Since 1987, patients at Thomas Jefferson University Hospital have been offered IORT in an attempt to improve their survival. METHODS: The authors reviewed all patients treated at Thomas Jefferson University Hospital with pancreatic adenocarcinoma from 1987 to 1994. From this population, 14 patients were identified who received IORT in conjunction with curative surgery. Duration of hospital stay, perioperative complications, duration of postoperative ileus, and survival were assessed by retrospective review. RESULTS: Of the 14 patients, 6 were male and 8 were female. Patient median age was 61. Six patients had stage I disease, 2 had stage II, 6 had stage III. Two patients had total pancreatectomy, 2 had distal pancreatectomy, and the remaining had pancreaticoduodenectomy (Whipple resection). Median survival was 16 months with a 15.5% 5-year survival. Postoperative complications, duration of hospital stay, and duration of postoperative ileus were not adversely affected by the addition of IORT when compared to in-house control subjects. CONCLUSIONS: Intraoperative radiation therapy is a useful adjunct to surgical resection as treatment of pancreatic cancer. The authors' data suggested it can prolong median survival and long-term survival without adding significant morbidity.

Adenocarcinoma↗

Diaspirin cross-linked hemoglobin resuscitation of hemorrhage: comparison of a blood substitute with hypertonic saline and isotonic saline.

UNLABELLED: Resuscitation with tiny volumes of hypertonic solutions rapidly restores tissue perfusion while minimizing edema after hemorrhage and tissue trauma. METHODS: We compared an O2-carrying fluid, Diaspirin Cross-Linked Hemoglobin (DCLHb), to 7.5% NS/Dextran-70 (HTS) or 0.9% saline (NS) in a trauma (celiotomy) hemorrhage model. Anesthetized rats (n = 10/group) underwent a tracheotomy, placement of jugular vein and carotid artery catheters, and placement of an abdominal aortic flow probe. Rats were hemorrhaged (20 mL/kg) from t = 0-15 minutes, and were given NS (group I), 60 mL/kg, HTS (group II), 4 mL/kg, or DCLHb (group III), 4 mL/kg, from t = 15-30 minutes. Sampling mandated removal of an additional 10 mL/kg of blood during the 2-hour experiment. RESULTS: Mean arterial pressure was restored after hemorrhage in all groups. Oxygen delivery, which diminished dramatically after hemorrhage, was less than baseline in all groups after resuscitation. Oxygen consumption was restored in all groups after a sharp decrease during hemorrhage. Base deficit increased in the all groups but was greatest after normal saline or hypertonic saline resuscitation (t = 120 minutes; I = 12 +/- 0.4*, II = 13 +/- 0.5* c, III = 10 +/- 0.1*; * = p < 0.05 versus baseline value within group for groups I, II, and III; c = p < 0.05 group versus DCLHb (group II), by ANOVA). CONCLUSION: DCLHb restored mean arterial pressure and ameliorated the development of flow-dependent oxygen consumption. Base deficit, a reflection of systemic oxygen debt, was minimized with this blood substitute. DCLHb may represent a superior small volume resuscitative fluid after trauma and hemorrhage.

Animals↗

Phantom studies of triple photon absorptiometry and bone mineral measurement at a hip prosthesis.

The feasibility of using triple photon absorptiometry (TPA) for the measurement of bone mineral mass about a hip prosthesis was examined. A theoretical expression describing the variance of TPA measurements was verified using a triple photon source and phantom materials which simulate the soft tissue-bone mineral-metal prosthesis system. The expression for the variance was used to determine an optimized set of photon energies. It was shown that a precision of 3% could be obtained for reasonable measurement times using this optimized set of energies, and that TPA should be a feasible approach for measurement of bone mineral about a hip prosthesis.

Absorptiometry, Photon↗

Triple photon absorptiometry cannot correct for fat inhomogeneities in lumbar spine bone mineral measurements.

In vivo fat inhomogeneities can cause significant errors in measurements of lumbar spine mineral mass using dual photon absorptiometry. Extension to a triple photon technique to correct for the presence of fat is not possible because of the unacceptable increase of about a factor of 3,000 required in the radiation dose to yield sufficient transmitted photons for adequate precision.

Absorptiometry, Photon↗

The error due to fat inhomogeneity in lumbar spine bone mineral measurements.

Bone mineral mass measurements using dual photon absorptiometry rely on the assumption that fat thickness is constant within the region scanned by the photon beam. This assumption has been tested using both single and multiple slices from archived CT scans. In 26 patients, the difference in fat content between the bone and baseline measurement sites, the fat deviation, was found to vary from -2.7 to 18.7%. The median fat deviation was 4.4% which can lead to errors in measured lumbar spine bone mineral of 6 to 11%. Approximately one third of patients will have errors greater than 10%.

Adipose Tissue↗

Effect of scintillation camera nonuniformity on ejection fraction measurements.

A rotating cardiac phantom with three possible ejection fraction (EF) values was used in conjunction with a scintillation camera employing energy correction and count skim arithmetic for uniformity correction. Studies were collected with and without any correction, with the energy window of the analyzer set properly, and with the camera properly tuned. The uniformity was then degraded in one experiment by off-setting the analyzer window both high and low with respect to the primary photopeak and in another experiment by de-tuning a selected photomultiplier tube. In both experiments studies were taken with no correction enabled, and then with each of the correction options enabled. The results of both experiments show that ejection fraction values could be in error when the differential uniformity using National Electrical Manufacturers Association (NEMA) protocols exceeds 10%. If either energy correction alone, or energy correction combined with count skim correction is used, the ejection fraction values return to more acceptable values. Asymmetric windows, improper setting of the energy window or a badly tuned photomultiplier will likely result in poor analog images before the effect on ejection fraction measurements becomes evident. Uniformity correction devices do not adversely affect the numerical results obtained from these phantom studies, but should, nevertheless, be used with caution.

Computers↗

Coherent scattering and bone mineral measurement: the dependence of sensitivity on angle and energy.

The sensitivity of a technique for the measurement of trabecular bone mineral concentration has been examined theoretically and experimentally. The technique is based on coherent gamma ray scattering and corrections for attenuation are obtained from transmitted photons rather than Compton scattered photons. For an incident photon energy of 60 keV, the minimum detectable bone mineral difference is practically independent of scattering angle while for an incident energy of 100 or 122 keV the scattering angle must be less than 70 degrees to optimize the minimum detectable difference.

Bone Density↗

A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo.

A model based upon steady-state diffusion theory which describes the radial dependence of diffuse reflectance of light from tissues is developed. This model incorporates a photon dipole source in order to satisfy the tissue boundary conditions and is suitable for either refractive index matched or mismatched surfaces. The predictions of the model were compared with Monte Carlo simulations as well as experimental measurements made with tissue simulating phantoms. The model describes the reflectance data accurately to radial distances as small as 0.5 mm when compared to Monte Carlo simulations and agrees with experimental measurements to distances as small as 1 mm. A nonlinear least-squares fitting procedure has been used to determine the tissue optical properties from the radial reflectance data in both phantoms and tissues in vivo. The optical properties derived for the phantoms are within 5%-10% of those determined by other established techniques. The in vivo values are also consistent with those reported by other investigators.

Diffusion↗