Biomedical subjects

Anthony J Fitzgerald

Publications and source records attributed to Anthony J Fitzgerald.

9 recordsLinked to original sources

PubMed2006

Terahertz pulsed imaging of human breast tumors.

The feasibility of using terahertz pulsed imaging to map margins of exposed breast tumors was investigated by imaging 22 excised human breast tissue specimens with carcinoma excised from 22 women (mean age, 59 years; range, 39-80 years). The study was approved by the local ethics research committee, and informed consent was obtained from all patients. The size and shape of tumor regions on terahertz images were compared with those identified at histopathologic examination of the imaged section. Two image parameters were investigated: the minimum of the terahertz impulse function and the ratio of the minimum to the maximum of the terahertz impulse function. The correlation coefficient for the tumor area on images compared with that on a photomicrograph of all 22 samples was greater than 0.82 for both parameters. The shape of the tumor regions on terahertz images also correlated well with that on a photomicrograph (median Spearman rank correlation coefficient, 0.69). Findings of this study demonstrate the potential of terahertz pulsed imaging to depict both invasive breast carcinoma and ductal carcinoma in situ under controlled conditions and encourage further studies to determine the sensitivity and specificity of the technique.

Adult↗

PubMed2006

Effects of mouse and human lipocalin homologues 24p3/lcn2 and neutrophil gelatinase-associated lipocalin on gastrointestinal mucosal integrity and repair.

BACKGROUND & AIMS: The lipocalin superfamily, including the mouse and human homologues 24p3/lcn2 and neutrophil gelatinase-associated lipocalin, show great functional diversity including roles in olfaction, transportation, and prostaglandin synthesis in mammals. Their potential role in maintaining gastrointestinal mucosal integrity and repair is, however, unclear. METHODS: Changes in 24p3/lcn2 expression in the mouse gut in response to various noxious agents were examined using Northern blot, in situ hybridization, and immunohistochemistry. Effects of recombinant 24p3/lcn2 on proliferation ([3H]-thymidine uptake), and restitution (cell-wounding migration) were assessed using human colonic HT29 and HCT116 cells. In addition, the effects of recombinant 24p3/lcn2 on the amount of gastric damage were assessed in rats treated with indomethacin (20 mg/kg) and restraint. RESULTS: Marked up-regulation of expression of 24p3/lcn2 was seen throughout the gut in response to indomethacin or dextran sodium sulfate treatment. Expression was increased particularly in the surface epithelial cells and infiltrating inflammatory cells. Proliferation and restitution assays in the presence of recombinant wild-type sequence neutrophil gelatinase-associated lipocalin, wild-type cys(98)-24p3/lcn2, and mutant ala98-24p3/lcn2 showed that all 3 peptides caused a 3- to 4-fold increase in promigratory activity (P < .01 vs control) but did not influence proliferation. The administration of wild-type cys98-, or mutant ala98-24p3/lcn2 (25 and 50 microg/kg/h, respectively), given via the subcutaneous route, both caused similar reductions in the rat gastric damage model (60% reduction at highest dose, P < .01 vs control), although oral administration was ineffective. CONCLUSIONS: 24p3/lcn2 facilitates mucosal regeneration by promoting cell migration.

Acute-Phase Proteins↗

PubMed2006

Terahertz pulsed spectroscopy of human Basal cell carcinoma.

Good contrast is seen between normal tissue and regions of tumor in terahertz pulsed imaging of basal cell carcinoma (BCC). To date, the source of contrast at terahertz frequencies is not well understood. In this paper we present results of a spectroscopy study comparing the terahertz properties (absorption coefficient and refractive index) of excised normal human skin and BCC. Both the absorption coefficient and refractive index were higher for skin that contained BCC. The difference was statistically significant over the range 0.2 to 2.0 THz (6.6 cm(-1) to 66.6 cm(-1)) for absorption coefficient and 0.25 to 0.90 THz (8.3 cm(-1) to 30 cm(-1)) for refractive index. The maximum difference for absorption was at 0.5 THz(16.7 cm(-1)). These changes are consistent with higher water content. These results account for the contrast seen in terahertz images of BCC and explain why parameters relating to the reflected terahertz pulse provide information about the lateral spread of the tumor. Knowing the properties of the tissue over the terahertz frequency range will enable the use of mathematical models to improve understanding of the terahertz response of normal and diseased tissue.

Basal Cell Carcinoma↗

PubMed2005

Nondestructive analysis of tablet coating thicknesses using terahertz pulsed imaging.

An understanding of the finished structure of complex pharmaceutical coating is becoming desirable, because tablet coatings are now one of the preferred routes to control the release of active pharmaceutical ingredients. There are few nondestructive techniques capable of examining the coatings of compressed tablets; for example laser induced breakdown spectroscopy has been used but this is a destructive method. Terahertz pulsed imaging offers a potential technique to examine coatings quickly and nondestructively. In the study reported herein, it was possible to distinguish between two brands of across-the-counter ibuprofen tablets. The terahertz maps obtained were compared with obtained photographs of cut-through sections; there was good agreement. The technique is fast: a waveform can be obtained in <20 ms allowing the technique to be considered as a candidate for on-line or at-line analysis in a process analytical environment. The lateral resolution of the technique is limited by diffraction of the terahertz focus to about 150 microm at 3 THz, whereas the axial resolution is limited by the terahertz pulse duration, which is <200 fs, to about 30 microm.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Modelling the propagation of terahertz radiation through a tissue simulating phantom.

Terahertz (THz) frequency radiation, 0.1 THz to 20 THz, is being investigated for biomedical imaging applications following the introduction of pulsed THz sources that produce picosecond pulses and function at room temperature. Owing to the broadband nature of the radiation, spectral and temporal information is available from radiation that has interacted with a sample; this information is exploited in the development of biomedical imaging tools and sensors. In this work, models to aid interpretation of broadband THz spectra were developed and evaluated. THz radiation lies on the boundary between regions best considered using a deterministic electromagnetic approach and those better analysed using a stochastic approach incorporating quantum mechanical effects, so two computational models to simulate the propagation of THz radiation in an absorbing medium were compared. The first was a thin film analysis and the second a stochastic Monte Carlo model. The Cole-Cole model was used to predict the variation with frequency of the physical properties of the sample and scattering was neglected. The two models were compared with measurements from a highly absorbing water-based phantom. The Monte Carlo model gave a prediction closer to experiment over 0.1 to 3 THz. Knowledge of the frequency-dependent physical properties, including the scattering characteristics, of the absorbing media is necessary. The thin film model is computationally simple to implement but is restricted by the geometry of the sample it can describe. The Monte Carlo framework, despite being initially more complex, provides greater flexibility to investigate more complicated sample geometries.

Diagnostic Imaging↗

PubMed2004

Multispectral classification techniques for terahertz pulsed imaging: an example in histopathology.

Terahertz pulsed imaging is a spectroscopic imaging modality using pulses of electromagnetic radiation (100 GHz-10 THz), and there has been recent interest in studying biomedical specimens. It is usual to display parametric images derived from the measured pulses. In this work, classification was achieved by applying multispectral clustering techniques to sets of parametric images. It was hypothesised that adequate information for clustering was carried in a small number of parametric images, providing these were weighted by complementary physical properties. Materials prepared for histopathological examination were chosen because their condition remained stable during long imaging periods and because their dehydrated state led to greater penetration of the radiation. Two specimens were examined in this pilot study, one of basal cell carcinoma and one of melanoma. Unsupervised ISODATA classification using three selected parametric terahertz pulsed images was compared qualitatively with k-means classification using the shape of the whole time series, and with conventional stained microscope slides. There was good qualitative agreement between the classifications. Classifications were consistent with the morphological appearances expected, but further work is required to determine if tumour discrimination is possible. The results have implications for the future development of the technique as the need for only a small number of features could lead to considerably reduced acquisition times.

Algorithms↗

PubMed2004

Terahertz pulsed imaging and spectroscopy for biomedical and pharmaceutical applications.

Terahertz (THz) radiation lies between the infrared and microwave regions of the electromagnetic spectrum. Advances in THz technology have opened up many opportunities in this scientifically and technologically important spectroscopic region. The THz frequency range excites large amplitude vibrational modes of molecules as well as probing the weak interactions between them. Here we describe two techniques that utilize THz radiation, terahertz pulsed imaging (TPI) and terahertz pulsed spectroscopy (TPS). Both have a variety of possible applications in biomedical imaging and pharmaceutical science. TPI, a non-invasive imaging technique, has been used to image epithelial cancer ex vivo and recently in vivo. The diseased tissue showed a change in absorption compared to normal tissue, which was confirmed by histology. To understand the origins of the differences seen between diseased and normal tissue we have developed a TPS system. TPS has also been used to study solids of interest in the pharmaceutical industry. One particularly interesting example is ranitidine hydrochloride, which is used in treatment of stomach ulcers. Crystalline ranitidine has two polymorphic forms known as form 1 and form 2. These polymorphs have the same chemical formula but different crystalline structure that give rise to different physiochemical properties of the material. Using TPS it is possible to rapidly distinguish between the two polymorphic forms.

Algorithms↗

PubMed2002

Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage.

Ischemia/reperfusion of mesenteric vessels is a useful model for acute vascular insufficiency and the early stages of multiorgan failure, conditions associated with high morbidity and mortality. Epidermal growth factor (EGF) is a potent mitogen that shows potential for use in intestinal injury. We therefore examined its influence on this model. Male Sprague-Dawley rats received human recombinant EGF (2 mg/kg i.p., n = 14) or saline (n = 16); 25 minutes before arterial clamping of the superior mesenteric artery (ischemic period) for 60 minutes followed by a final 60-minute reperfusion period. Additional rats were not operated on (controls, n = 7) or had sham operation (laparotomy only, n = 10). Ischemia/reperfusion caused macroscopic damage affecting 56%, 51 to 67% (median, interquartile range), of small intestinal length and intraluminal bleeding. Malondialdehyde levels (free radical marker) increased eightfold compared to nonoperated animals (2400, 2200 to 2700 micro mol/mg protein versus 290, 250 to 350 micro mol/mg protein, P < 0.01) and myeloperoxidase levels (marker for inflammatory infiltrate) increased 15-fold (3150, 2670 to 4180 U/g tissue versus 240, 190 to 250 U/g tissue, P < 0.01). Pretreatment with EGF reduced macroscopic injury to 11%, 0 to 15%; prevented intraluminal bleeding; and reduced malondialdehyde and myeloperoxidase levels by approximately 60% and 90% (all P < 0.01 versus non-EGF-treated). Mesenteric ischemia/reperfusion also damaged the lungs and kidneys and increased serum tumor necrosis factor-alpha levels (circulating cytokine activity marker). EGF pretreatment also reduced these changes. These studies provide preliminary evidence that EGF is a novel therapy for the early treatment or prevention of intestinal damage and multiorgan failure resulting from mesenteric hypoperfusion.

Animals↗

PubMedDate not supplied

Simulating the response of terahertz radiation to basal cell carcinoma using ex vivo spectroscopy measurements.

Studies of basal cell carcinoma using terahertz pulsed imaging have revealed a significant difference between regions of tumor and healthy tissue. These differences are manifested in the reflected pulse due to what is thought to be changes in refractive index and absorption. We present measurements of the refractive index and absorption coefficient of excised normal tissue and basal cell carcinoma using terahertz (THz) transmission spectroscopy. We extract Debye parameters from these data and enter them into a finite difference time domain simulation to predict the shape of the waveforms reflected off the normal tissue and basal cell carcinoma and compare them with published in vivo data. Simulating the interaction of terahertz radiation with normal and cancerous tissue is a key step toward understanding the origin of contrast in terahertz images of skin cancer.

Basal Cell Carcinoma↗