Simulation of scanning laser techniques for optical imaging of blood-related intrinsic signals

Optical imaging of intrinsic signals detects neural activation patterns by taking video images of the local activity-related changes in the light intensity reflected from neural tissue (intrinsic signals). At red light (605 nm), these signals are caused mainly by local variations of the tissue absorption following deoxygenation of blood. We characterize the image generation process during optical imaging by Monte Carlo simulations of light propagation through a homogeneous model tissue equipped with a local absorber. Conventional video imaging and scanning laser imaging are compared. We find that, compared with video imaging, scanning laser techniques drastically increase both the contrast and the lateral resolution of optical recordings. Also, the maximum depth up to which the signals can be detected is increased by roughly a factor of 2 when scanning laser optical imaging is used. Further, the radial profile of the diffuse-reflectance pattern for each pixel is subject to changes that correlate with the depth of the absorber within the tissue. We suggest a detection geometry for the online measurement of these radial profiles that can be realized by modifying a standard scanning laser ophthalmoscope.     

Quantification of plasma hemoglobin in the presence of bilirubin with bilirubin oxidase

Owing to the overlapping absorption bands of hemoglobin and bilirubin, spectrophotometric determination of plasma free hemoglobin has been plagued by the interference of bilirubin when the latter is present in significant concentrations. To resolve this problem, bilirubin oxidase from Myrothecium verrucaria has been used to remove bilirubin in icteric samples. The enzyme converts bilirubin to biliverdin and eliminates its absorption in the 400 nm region. The absorbance of hemoglobin at 415 nm after Allen baseline correction is used to quantify its concentration. Intra-assay precision of this method on a sample containing 200 mg/L of free hemoglobin and 200 mg/L of bilirubin is 3.1 percent (n = 10), while the between-run precision is 3.8 percent (n = 10). Accuracy studies with samples containing 200 mg/L of bilirubin yielded a straight line: y = 0.90x + 2.31, Sy.x = 3.3, r = 0.99. These results demonstrate that this method can be used to determine free hemoglobin in icteric specimens.     

Non-invasive measurements of breast tissue optical properties using frequency-domain photon migration

A multiwavelength, high bandwidth (1 GHz) frequency-domain photon migration (FDPM) instrument has been developed for quantitative, non-invasive measurements of tissue optical and physiological properties. The instrument produces 300 kHz to 1 GHz photon density waves (PDWs) in optically turbid media using a network analyser, an avalanche photodiode detector and four amplitude-modulated diode lasers (674 nm, 811 nm, 849 nm, and 956 nm). The frequency of PDW phase and amplitude is measured and compared to analytically derived model functions in order to calculate absorption, mu a, and reduced scattering, mu s, parameters. The wavelength-dependence of absorption is used to determine tissue haemoglobin concentration (total, oxy- and deoxy- forms), oxygen saturation and water concentration. We present preliminary results of non-invasive FDPM measurements obtained from normal and tumour-containing human breast tissue. Our data clearly demonstrate that physiological changes caused by the presence of small (about 1 cm diameter) palpable lesions can be detected using a handheld FDPM probe.     

Optical coherence tomography for neurosurgical imaging of human intracortical melanoma

OBJECTIVE: Intraoperative identification of brain tumors and tumor margins has been limited by either the resolution of the in vivo imaging technique or the time required to obtain histological specimens. Our objective was to evaluate the feasibility of using optical coherence tomography (OCT) as a high-resolution, real-time intraoperative imaging technique to identify an intracortical melanoma. INSTRUMENTATION: OCT is a new, noncontact, high-speed imaging technology capable of resolutions on the micrometer scale. OCT is analogous to ultrasound B-mode imaging, except that reflections of infrared light, rather than sound, are detected. OCT uses inherent tissue contrast, rather than enhancement with dyes, to differentiate tissue types. The compact, fiberoptic-based design is readily integrated with surgical instruments. METHODS: A portable handheld OCT surgical imaging probe has been constructed for imaging within the surgical field. Cadaveric human cortex with metastatic melanoma was harvested and imaged in two and three dimensions. Changes in optical backscatter intensity were used to identify regions of tumor and to locate tumor margins. Structures within the optical coherence tomographic images were compared with the histological slides. RESULTS: Two-dimensional images showed increased optical backscatter from regions of tumor, which was quantitatively used to determine the tumor margin. The images correlated well with the histological findings. Three-dimensional reconstructions revealed regions of tumor penetrating normal cortex and could be resectioned at arbitrary planes. Subsurface cerebral vascular structures could be identified and were therefore avoided. CONCLUSION: OCT can effectively differentiate normal cortex from intracortical melanoma based on variations in optical backscatter. The high-resolution, high-speed imaging capabilities of OCT may permit the intraoperative identification of tumor and the more precise localization of tumor margins.     

Hemoglobin values: comparative survey of the 1976 Canadian Olympic team

In view of the role of hemoglobin in oxygen transport, the hemoglobin concentration in whole blood may indicate readiness for maximal physical performance. Hemoglobin concentrations were determined in members of the 1976 Canadian Olympic team and compared with those of the 1975 Canadian general population and with published data for the 1968 Australian and Dutch Olympic teams. The mean hemoglobin concentrations of the 123 male and 64 female Canadian Olympic athletes were 14.7 +/- 1.0 and 12.9 +/- 0.7 g/dL, respectively. Both male and female Canadian Olympic athletes had significantly lower (P less than 0.01) values than the other three groups. The suboptimal hemoglobin concentrations may be related to inadequate dietary intake of protein and iron.     

Low-dose phase contrast x-ray medical imaging

Phase contrast x-ray imaging is a powerful technique for the detection of low-contrast details in weakly absorbing objects. This method is of possible relevance in the field of diagnostic radiology. In fact, imaging low-contrast details within soft tissue does not give satisfactory results in conventional x-ray absorption radiology, mammography being a typical example. Nevertheless, up to now all applications of the phase contrast technique, carried out on thin samples, have required radiation doses substantially higher than those delivered in conventional radiological examinations. To demonstrate the applicability of the method to mammography we produced phase contrast images of objects a few centimetres thick while delivering radiation doses lower than or comparable to doses needed in standard mammographic examinations (typically approximately 1 mGy mean glandular dose (MGD)). We show images of a custom mammographic phantom and of two specimens of human breast tissue obtained at the SYRMEP bending magnet beamline at Elettra, the Trieste synchrotron radiation facility. The introduction of an intensifier screen enabled us to obtain phase contrast images of these thick samples with radiation doses comparable to those used in mammography. Low absorbing details such as 50 microm thick nylon wires or thin calcium deposits (approximately 50 microm) within breast tissue, invisible with conventional techniques, are detected by means of the proposed method. We also find that the use of a bending magnet radiation source relaxes the previously reported requirements on source size for phase contrast imaging. Finally, the consistency of the results has been checked by theoretical simulations carried out for the purposes of this experiment.     

Circulation persistence and biodistribution of lyophilized liposome-encapsulated hemoglobin: an oxygen-carrying resuscitative fluid

OBJECTIVE: To evaluate the circulation persistence and organ biodistribution of a freeze-dried, oxygen carrying resuscitative fluid: liposome-encapsulated hemoglobin. DESIGN: Randomized, animal studies. SETTING: Accredited animal research facilities. SUBJECTS: Normal female Balb/c mice and male New Zealand rabbits. INTERVENTIONS: Two groups of normal female Balb/c mice were injected in the tail vein with either lyophilized liposome-encapsulated hemoglobin (n = 9) that was reconstituted just before administration, or with unlyophilized liposome-encapsulated hemoglobin (n = 9) as a comparison. Two groups of male New Zealand rabbits were injected in the ear vein with either lyophilized 99mTc-liposome-encapsulated hemoglobin (n = 6) or unlyophilized 99mTc-liposome-encapsulated hemoglobin as a comparison (n = 6). After injection, mice were anesthetized by brief inhalation of halothane followed by blood sampling through the retro-orbital sinus. Rabbits were anesthetized 30 mins before liposome-encapsulated hemoglobin administration with an intramuscular injection of a 5:1 mixture of ketamine (50 mg/kg) and xylazine (10 mg/kg). Rabbits were then dynamically imaged for 90 mins, housed, and at 20 hrs, imaging again followed by autopsy and tissue sampling to validate imaged organ biodistributions. MEASUREMENTS: Circulation persistence in the mouse was measured by removing a blood sample at various time points up to 24 hrs after injection. The blood sample was centrifuged in a hematocrit capillary tube and the disappearance of the sedimented liposome-encapsulated hemoglobin fraction was measured. The change in the sedimented fraction of the liposomes with time was used to generate circulation persistence profiles in mice. The circulation persistence and organ biodistribution of 99mTc-liposome-encapsulated hemoglobin was measured by circling regions of interest on computer-generated gamma camera images. These image intensities were then calculated as a function of total injected dose which was measured from a known volume and activity of 99mTc-liposome-encapsulated hemoglobin. Actual tissue uptake was estimated from images by subtracting blood pool contribution which was measured by injecting 99mTc-labeled rabbit red cells. Imaged organ biodistribution was validated at 20 hrs by measuring activity in weighed portions of tissue after autopsy. MAIN RESULTS: The mean circulation half-life of liposome-encapsulated hemoglobin in mice injected at a dose of 1.0 g phospholipid/kg mouse and 1.95 g hemoglobin/kg was approximately 10.4 +/- 0.5 (SD) hrs. The circulation half-life of lyophilized liposome-encapsulated hemoglobin was 10.7 +/- 0.7 hrs. The circulation profiles demonstrate a rapid removal phase over the first 4 hrs after injection, followed by a secondary slow removal measured up to 24 hrs. The rapid removal phase of liposome-encapsulated hemoglobin and lyophilized liposome-encapsulated hemoglobin in the rabbit (injected at the same dose) indicated that lyophilized liposome-encapsulated hemoglobin persists longer than the unlyophilized form in the first 4 hrs after injection. The organ biodistributions of unlyophilized 99mTc-liposome-encapsulated hemoglobin and lyophilized 99mTc-liposome-encapsulated hemoglobin in the rabbit demonstrate that the reticuloendothelial system is the primary site of removal, with significant uptake of lyophilized 99mTc-liposome-encapsulated hemoglobin by the liver (15.6 +/- 1.0%), bone marrow (12.6 +/- 1.6%), and spleen (9.7 +/- 1.1%). The kidneys showed little accumulation of unlyophilized 99mTc-liposome-encapsulated hemoglobin or lyophilized 99mTc-liposome-encapsulated hemoglobin (1.6 +/- 0.2% and 1.8 +/- 0.1%, respectively), an important result for the efficacy and safety of this hemoglobin-based blood substitute. (ABSTRACT TRUNCATED)     

Temporal sampling requirements for the tracer kinetics modeling of breast disease

The physiological parameters measured in the tracer kinetics modeling of data from a dynamic contrast-enhanced magnetic resonance (MR) breast exam (blood flow-extraction fraction product [FE], volume of the extracellular extravascular space [Ve], and blood volume [Vb]) may enable non-invasive diagnosis of breast cancer. One of the factors that compromises the accuracy and precision of the parameter estimates, and therefore their diagnostic potential, is the temporal resolution of the MR scans used to measure contrast agent (gadolinium-diethylenetriamine pentaacetic acid [Gd-DTPA]) concentration in an artery (arterial input function [AIF]) and in the tissue (tissue residue function [TRF]). Using computer simulations, we have examined, for several AIF widths, the errors introduced into estimates of tracer kinetic parameters in breast tissue due to insufficient temporal sampling. Temporal sampling errors can be viewed as uncertainties and biases in the parameter estimates introduced by the uncertainty in the relative alignments of the AIF, TRF, and sampling grid. These effects arise from the model's inherent sensitivity to error in either the AIF or TRF, which is dependent on the values of the tracer kinetic parameters and increases with AIF width. Based on the results of the simulations, to ensure that the error in FE and Ve will be under 10% of their true values, we recommend a rapid bolus injection of contrast agent (approximately 10 s), that the AIF be sampled every second, and that the TRF be sampled every 16 s or less. An accurate measurement of Vb requires that the TRF be sampled at least every 4 s. The results of these investigations can be used to set minimum dynamic imaging rates for tracer kinetics modeling of the breast.     

Optical investigations of physiology: a study of intrinsic and extrinsic biomedical contrast

The utility and performance of optical studies of tissue depends upon the contrast and the changes of contrast in health and disease and in functional activity. The contrast is determined both by the optical properties of extrinsic chromophores and scatterers but especially upon the changes evoked by physiological activity and pathological states. Here, we have focused upon absorption changes of the intrinsic probe, blood absorbance changes due to cortical hypoxia and to haematomas, giving, for particular conditions, absorbance changes of 0.15 and over 0.4 delta OD, respectively. Functional activity may give changes of blood volume of over 0.05 delta OD with some variability due to individual responses that is best expressed as histogram displays of the distribution of response among a significant population. Responses have been observed in prefrontal parietal and occipital functions (242 tests). Extrinsic probes afford signals dependent upon the dose tolerance of the subject and can readily equal or exceed the blood volume and oxygenation signals, and currently afford vascular volume and flow indications. However, contrast agents for the functional activity of cellular function are ultimately to be expected. Finally, light-scattering changes afford osmolyte-related responses and are here shown to indicate a larger signal attributed to cortical depolarization and K+ release in hypoxia/ischaemia. Thus, the optical method affords imaging of manifold contrasts that greatly enhance its specificity and sensitivity for diagnostic procedures.     

Effects of ambient light and view box luminance on the detection of calcifications in mammography

OBJECTIVE: Viewing conditions can affect diagnostic performance differently depending on background optical densities. We quantified detection accuracy when viewing calcifications in glandular tissue under recommended viewing conditions versus accuracy with lower view box luminance and higher ambient lighting. MATERIALS AND METHODS: A phantom with adipose, 50% adipose and 50% glandular, and glandular-simulating material was imaged, and images were interpreted by five medical imaging physicists using two lighting conditions: the recommended one, high view box luminance (4365 nits) with low ambient light (25 lx), and a suboptimal one, low view box luminance (1763 nits) with moderate ambient lighting (290 lx). Then, a dense (Breast Imaging Reporting and Data System breast composition pattern type 4) unfixed cadaveric breast with numerous native calcifications was imaged 28 times. Nineteen of the films had added clusters of simulated calcifications. Three radiology fellows, each with 11 months of training in mammography, identified the added calcification clusters in the images under the two lighting conditions. Changes in phantom analysis and accuracy of the clinical diagnosis were compared for each lighting condition. RESULTS: On mammograms of the phantom, both speck and fibril identification were degraded by an average of 1.4 objects for the adipose-simulating section (with its darker optical density). For medium optical densities, found in the section with the simulation of 50% glandular and 50% adipose tissue, suboptimal lighting conditions had little or no effect on speck and fibril identification. For sections of the phantom that simulated glandular tissue, an average of 0.6 specks or fibers were not seen when lighting was suboptimal. With the dense cadaveric breast, the fraction of added calcification clusters detected by the three observers improved by an average of 17% when low luminance viewers and high ambient light were replaced with recommended viewing conditions; individual scores of the observers improved significantly: p values ranged from .02 to .05. CONCLUSION: Luminance of the view box and ambient lighting significantly affect detection of calcifications in dense breasts when images are interpreted by radiologists with about 1 year of training in mammography. Detection of calcifications in phantoms is primarily degraded for adipose tissue with its darker optical density. However, when lighting conditions are suboptimal, some observers also have trouble detecting calcifications in glandular tissue with its low optical density.     

Paramagnetic liposomes as magnetic resonance imaging contrast agents. Assessment of contrast efficacy in various liver models

RATIONALE AND OBJECTIVES: Liposomal gadolinium (Gd)-HP-DO3A has been evaluated as a contrast agent for liver magnetic resonance imaging. The influence of various liposomal physicochemical properties on the liver uptake and contrast efficacy was investigated in various ex vivo and in vivo liver models. METHODS: Liposomes of different size and membrane properties were prepared. The liposome size ranged from 74 to 304 nm. Two types of phospholipid compositions were studied; a mixture of hydrogenated phosphatidylcholine (HPC) and hydrogenated phosphatidylserine (HPS) with a phase transition temperature (Tm) of 51 degrees C and, a blend composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) displaying a Tm of 41 degrees C. Ex vivo tissue relaxometry and in vivo liver imaging were used to study the influence of liposome composition on the liver uptake and contrast efficacy of intravenously injected liposomes. The influence of liposome size and composition on the kinetics of liver uptake and imaging effect was assessed ex vivo in the perfused rat liver. RESULTS: The HPC/HPS preparations showed generally a higher and faster liver uptake than the DPPC/DPPG preparations due to a higher stability in blood/perfusate (high Tm) and to the HPS component. The liposome size modulated the extent and kinetics of liver uptake; the larger the size, the faster and more extensive was the liver uptake. Both types of liposome preparations were shown to be efficient liver susceptibility agents both ex vivo and in vivo due to their uptake by the Kupffer cells of liver. The lack of full correlation between the extent of liver uptake and degree of contrast enhancement might be attributed to different regimes of susceptibility-based relaxation. CONCLUSIONS: The present study has demonstrated the influence of key liposomal physicochemical properties on the liver uptake and contrast efficacy of liposome-encapsulated Gd chelates, exemplified by Gd-HP-DO3A.     

Histopathology of human coronary atherosclerosis by quantifying its chemical composition with Raman spectroscopy

BACKGROUND: Lesion composition, rather than size or volume, determines whether an atherosclerotic plaque will progress, regress, or rupture, but current techniques cannot provide precise quantitative information about lesion composition. We have developed a technique to assess the pathological state of human coronary artery samples by quantifying their chemical composition with near-infrared Raman spectroscopy. METHODS AND RESULTS: Coronary artery samples (n=165) obtained from explanted recipient hearts were illuminated with 830-nm infrared light. Raman spectra were collected from the tissue and processed to quantify the relative weights of cholesterol, cholesterol esters, triglycerides and phospholipids, and calcium salts in the examined artery location. The artery locations were then classified by a pathologist and grouped as either nonatherosclerotic tissue, noncalcified plaque, or calcified plaque. Nonatherosclerotic tissue, which included normal artery and intimal fibroplasia, contained an average of approximately 4+/-3% cholesterol, whereas noncalcified plaques had approximately 26+/-10% and calcified plaques approximately 19+/-10% cholesterol in the noncalcified regions. The average relative weight of calcium salts was 1+/-2% in noncalcified plaques and 41+/-21% in calcified plaques. To make this quantitative chemical information clinically useful, we developed a diagnostic algorithm, based on a first set of 97 samples, that demonstrated a strong correlation of the relative weights of cholesterol and calcium salts with histological diagnoses of the same locations. This algorithm was then prospectively tested on a second set of 68 samples. The algorithm correctly classified 64 of these new samples, thus demonstrating the accuracy and robustness of the method. CONCLUSIONS: The pathological state of a given human coronary artery may be assessed by quantifying its chemical composition, which can be done rapidly with Raman spectroscopic techniques. When Raman spectra are obtained clinically via optical fibers, Raman spectroscopy may be useful in monitoring the progression and regression of atherosclerosis, predicting plaque rupture, and selecting proper therapeutic intervention.     

Tumor imaging with a macromolecular paramagnetic contrast agent: gadopentetate dimeglumine-polylysine

RATIONALE AND OBJECTIVES: We evaluated magnetic resonance (MR) contrast enhancement of tumor tissue following injection of the macromolecular conjugate, gadopentetate dimeglumine-polylysine. METHODS: T1-weighted MR imaging scans were performed on female Fisher-344 rats with subcutaneously implanted mammary adenocarcinoma tumors. Following the baseline scan, gadopentetate dimeglumine-polylysine or gadopentetate dimeglumine was injected at a dose of 0.1 mmol gadolinium per kilogram. RESULTS: Gadopentetate dimeglumine-polylysine injection resulted in a maximum enhancement of tumor contrast of 310 +/- 60% (n = 7). Tumor tissue remained enhanced and well defined for several days after gadopentetate dimeglumine-polylysine injection. Gadopentetate dimeglumine injection at the same dose resulted in a 70 +/- 25% (n = 4) maximal tumor enhancement and a corresponding 25 +/- 4% muscle enhancement. CONCLUSION: Gadopentetate dimeglumine-polylysine provides higher, more sustained tumor contrast than does gadopentetate dimeglumine for the same dosage of gadolinium.     

Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET

[Carbonyl-11C]WAY-100635 is a promising PET radioligand for the 5-HT1A receptor, having demonstrated more favorable characteristics for in vivo imaging than the previously available [O-methyl-11C]WAY-100635. The current study evaluates different tracer kinetic modelling strategies for the quantification of 5-HT1A receptor binding in human brain. Mathematical modelling of the carbonyl-labeled radiotracer is investigated using compartmental structures, including both plasma input and reference tissue approaches. Furthermore, the application of basis function methods allows for the investigation of parametric imaging, providing functional maps of both delivery and binding of the radioligand. Parameter estimates of binding from normal volunteers indicate a low intra- versus a high intersubject variability. It is concluded that a simplified reference tissue approach may be used to quantify 5-HT1A binding either in terms of ROI data or as parametric images.     

Mammographic densities and breast cancer risk

The radiological appearance of the female breast varies among individuals because of differences in the relative amounts and X-ray attenuation characteristics of fat and epithelial and stromal tissues. Fat is radiolucent and appears dark on a mammogram, and epithelium and stroma are radiodense and appear light. We review here the evidence that these variations, known as mammographic parenchymal patterns, are related to risk of breast cancer. Studies that used quantitative measurement to classify mammographic patterns have consistently found that women with dense tissue in more than 60-75% of the breast are at four to six times greater risk of breast cancer than those with no densities. These risk estimates are independent of the effects of other risk factors and have been shown to persist over at least 10 years of follow up. Estimates of attributable risk suggest that this risk factor may account for as many as 30% of breast cancer cases. Mammographically dense breast tissue is associated both with epithelial proliferation and with stromal fibrosis. The relationship between these histological features and risk of breast cancer may by explained by the known actions of growth factors that are thought to play important roles in breast development and carcinogenesis. Mammographically dense tissue differs from most other breast cancer risk factors in the strength of the associated relative and attributable risks for breast cancer, and because it can be changed by hormonal and dietary interventions. This risk factor may be most useful as a means of investigating the etiology of breast cancer and of testing hypotheses about potential preventive strategies.     

Plasma hemoglobin measurement techniques for the in vitro evaluation of blood damage caused by medical devices

A sensitive measure of the in vitro blood damage potential of a medical device is the rate at which hemoglobin is released into the plasma from red blood cells flowing through the device. Presently there is no one widely accepted method for measuring the plasma hemoglobin concentration. Nine currently used assays, classified as either direct optical or added chemical techniques, were evaluated for accuracy, reproducibility, sensitivity, interference effects, and ease of use by adding hemoglobin (1-200 mg/dl) to saline, lipid, and bilirubin solutions and to normal cow plasma. Most of the assays displayed good linearity, accuracy, and reproducibility down to 1 mg/dl when interferents were absent. However, representative of the effects caused by interferents, the endogenous hemoglobin concentration of a typical cow plasma sample measured by the 9 techniques ranged from -2 to 39 mg/dl. Although used by fewer organizations, some of the direct optical spectrophotometric methods (e.g., the Cripps and Harboe baseline correction methods) are safer, easier, and more precise and accurate than the chemical addition methods used to measure plasma hemoglobin concentration from in vitro blood damage testing of medical devices.     

Breast carcinoma: MR imaging before re-excisional biopsy

PURPOSE: To investigate the role of magnetic resonance (MR) imaging in the examination of patients after excisional biopsy of breast carcinoma before re-excision. MATERIALS AND METHODS: Forty-seven patients underwent contrast material-enhanced MR imaging after initial excisional biopsy of breast carcinoma before further surgery. RESULTS: The positive predictive value of MR imaging for predicting residual disease was 82%; the negative predictive value was 61%. Fourteen patients had multifocal (n = 6) or diffuse (n = 8) carcinoma. The extent of tumor was correctly identified with MR imaging alone in nine of the 14 patients, with both mammography and MR imaging in three patients, with mammography alone in one patient, and with no imaging modality in one patient. In four of the 14 patients, management was altered from re-excision to mastectomy (n = 3) or from breast-conservation therapy to mastectomy (n = 1). CONCLUSION: MR imaging has a high positive predictive value for predicting residual tumor after excisional biopsy. The identification of mammographically and clinically unsuspected multifocal or extensive residual tumor may lend support for mastectomy rather than re-excision. However, false-negative findings due to postsurgical changes and false-positive findings due to enhancement of granulation tissue and benign breast tissue remain limitations.     

MnPcS4: a new MRI contrast enhancing agent for tumor localisation in mice

Manganese-tetrasulfonated phthalocyanine (MnPcS4) has been evaluated as a potential contrast agent in Magnetic resonance imaging (MRI) for tumor localisation in mice. MnPcS4 showed favourable molar relaxivity, much better than Gd-DTPA and comparable to tetrasulfonated manganese complex of porphyrin (TPPS4). Tumors showed selective retention of the metal complex (dye) with the peak value reached at 24 hours following intravenous administration. Dye concentration in tumors remained consistently higher than either kidney or muscle tissue both at 1 and 24 hours and a 10-fold increase in tumor-to-muscle ratio over the control was seen at 24 hr. Normal liver tissue, however, showed higher concentration than tumor at all times during the study. A linear correlation was found between longitudinal relaxation rate (1/T1) and the corresponding concentration of MnPcS4 in various tissues. MR imaging done in animals using 1.5 T superconducting clinical imager showed a mean percent increase in signal intensity of 131.8% (SD +/- 32.86) in the tumor and a 70% increase in tumor-to-muscle ratio over the pretreatment value, at 24 hr. The results suggest that MnPcS4 is a potential tumor-selective contrast agent in MRI.     

Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene

BACKGROUND AND OBJECTIVES: Proteoglycans of the extracellular matrix are vital to the growth and evolution of malignant neoplasms. The present study determined the composition of proteoglycans isolated from paired specimens of normal breast and adenocarcinoma of the breast harvested from each patient (n = 8). The proteoglycans were then tested for their ability to stimulate endothelial cell proliferation. METHODS: Proteoglycans were isolated by extraction with 4 M guanidine hydrochloride and purified by CsCl density-gradient centrifugation. The proteoglycans were characterized and tested for their ability to simulate endothelial cell proliferation. RESULTS: In each case, the total proteoglycan content of the tumor was significantly greater than that of the corresponding normal tissue. The proteoglycans isolated from the carcinoma contained 32.2% (13.7/42.5) more chondroitin sulfate, 18.5% (5.6/30.2) less dermatan sulfate, and 29.6% (8.1/27.3) less heparan sulfate than did the proteoglycans of normal breast tissue. Proteoglycans from normal tissue did not stimulate endothelial cell proliferation, whereas those from malignant tissue stimulated proliferation by 1.3- to 1.5-fold. CONCLUSIONS: These results indicate that malignant breast tissue exhibits both qualitative and quantitative changes in proteoglycan composition, which, in turn, may stimulate endothelial cell proliferation.     

Efficacy of dynamic susceptibility contrast MRI using echo-planar imaging in differential diagnosis of breast tumors

It has been shown that T1-weighted dynamic MR imaging is a useful method in differentiating malignant breast tumors from benign lesions. Invasive breast carcinomas enhance more rapidly than benign lesions such as fibroadenomas, papillomas, and proliferative fibrocystic diseases. However, significant overlap in the dynamic profile of benign and malignant lesions may occur, resulting in relatively low specificity, which is an inherent limitation of this technique. The author attempted to improve diagnostic accuracy by utilizing dynamic susceptibility contrast MR imaging (DSC-MRI) with a single-shot echo-planar imaging sequence. Twenty-two patients underwent DSC-MRI using a 1.5-T unit (Magnetom Vision, Siemens). Images were obtained before, during and after the bolus injection of 20 mL of gadopentetate dimeglumine. The signal reduction rate within the first 30 seconds (delta RT2) was calculated by the following equation: delta RT2 = (postcontrast signal intensity-precontrast signal intensity)/precontrast signal intensity. A rapid, strong decrease in signal intensity was observed on the first pass of the contrast material in all cases of carcinoma, whereas no or only a minimal decrease in signal intensity was observed in all but one of the benign lesions. This method seems to be more accurate than T1-weighted dynamic MR imaging in the differentiation benign and malignant breast lesions. Since DSC-MRI can be performed quickly, subsequent conventional T1-weighted imaging can provide additional information about the morphologic features of lesions, to further support the diagnosis. In conclusion, DSC-MRI seems to be a promising method for the accurate preoperative assessment of breast lesions.