Analytical methods in biotechnology: introduction.
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Biomedical subjects
Publications and source records attributed to C R Hill.
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We review the current state of knowledge of the processes by which the information content of ultrasonic pulse-echo images is transferred to an observer, to the point of contributing to diagnostic judgments. As systematic knowledge in this specific field is rather sparse, we present relevant information and techniques derived from other areas of image science, both medical and otherwise. Quantitative measures both of the information content of ultrasonic and other images and of their characteristic noise content are first considered. An account is then given of the relevant aspects of human visual psychophysics, with particular reference to perception of contrast and detail, image texture, movement and colour, again with emphasis on documenting quantitative aspects of such behaviour. Against this background, we consider the efficiency, in current practice, of image information transfer to a human observer, how and to what extent this could be improved by changes in practice and, in particular, in what situations substantial innovations in machine processing of image data would be expected to improve human performance. It is suggested that several problems in the field may provide a worthwhile and challenging scope for future research.
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BACKGROUND AND METHODS: Inositol is a major component of the intracellular mediators of insulin action. To investigate the possible role of altered inositol metabolism in non-insulin-dependent diabetes mellitus (NIDDM), we used gas chromatography and mass spectrometry to measure the myo-inositol and chiro-inositol content of urine specimens from normal subjects and patients with NIDDM: The study subjects were whites, blacks, and Pima Indians. The type of inositol and its concentration in insulin-mediator preparations from muscle-biopsy specimens from normal subjects and diabetic patients were also determined. RESULTS: The urinary excretion of chiro-inositol was much lower in the patients with NIDDM (mean [+/- SE], 1.8 +/- 0.8 mumol per day) than in the normal subjects (mean, 84.9 +/- 26.9 mumol per day; P less than 0.01). In contrast, the mean urinary myo-inositol excretion was higher in the diabetic patients than in the normal subjects (444 +/- 135 vs. 176 +/- 46 mumol per day; P less than 0.05). There was no correlation between chiro-inositol excretion and the age, sex, or weight of the diabetic patients, nor was there any correlation between urinary chiro-inositol and myo-inositol excretion in either group. The results were similar in a primate model of NIDDM, and chiro-inositol excretion was decreased to a lesser extent in animals with prediabetic insulin resistance. chiro-Inositol was undetectable in insulin-mediator preparations from muscle-biopsy samples obtained from patients with NIDDM: Similar preparations from normal subjects contained substantial amounts of chiro-inositol. Furthermore, the chiro-inositol content of such preparations increased after the administration of insulin during euglycemic-hyperinsulinemic-clamp studies in normal subjects but not in patients with NIDDM: CONCLUSIONS: NIDDM is associated with decreased chiro-inositol excretion and decreased chiro-inositol content in muscle. These abnormalities seem to reflect the presence of insulin resistance in NIDDM:
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For the purpose of assessing and comparing the practical performance of various specific approaches to quantitative tissue characterisation, three sets of performance criteria are proposed, relating respectively to contrast resolution, spatial resolution, and speed of presentation. In each case numerical performance targets are suggested: in particular that spatial resolution should preferably be within a linear factor of three of the best achievable anatomical resolution of the associated imaging techniques and that presentation speed should be 'real time' (i.e. about 10 Hz). In the light of these criteria and performance targets the main existing approaches to ultrasonic tissue characterisation are then considered. These are classified in two groups: first those approaches based on measurements of bulk properties of tissues and secondly those related to parameters of the structural organisation of tissues. Examination of available evidence suggests that the latter group are more promising than the former. Finally it is argued that ultrasonic methods of tissue characterisation have substantial practical potential but that the realisation of such potential is contingent on achieving consensus on choice of a single, optimised and generally applicable approach that would carry with it the linked benefits of industrial standardisation and broad sharing of clinical experience.
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We assessed the contribution of the hippocampal formation to performance in tasks that require rats to respond to a relationship between discriminative stimuli. The first experiment employed a nonmatching-to-sample procedure in a Y-maze. Three pairs of boxes were used which differed in brightness of the walls and in the odors that they contained. The rats were trained prior to receiving kainic acid and colchicine-induced damage to the hippocampal formation or electrolytic damage to the amygdala. After surgery all rats performed the nonmatching-to-sample task accurately if both brightness and odor cues were present in the sample and choice boxes or if the boxes contained either visual cues alone or odor cues alone. If the available cue modality was different in sample and choice boxes, then the amygdala-damaged, but not the hippocampal-damaged, rats performed accurately. In the second experiment control rats or rats with hippocampal formation damage were trained postoperatively in a conditional black/white discrimination task in a Y-maze. Only the control group successfully learned to select the white arm if the start box was illuminated and the black arm if the start box was dark. Subsequently, both groups learned a simple black/white discrimination. The same rats were tested in the hidden platform version of the Morris water task and only the control group learned to swim accurately to the goal. Both groups learned to swim accurately to a visible black platform. The results are consistent with the notion that the hippocampal formation is essential to learning that involves control exerted by a configural relationship among cues, independently of the spatial or conditional requirements of tasks.
An analysis is made of the kinetics of human liver parenchyma in response to mechanical impulses arising in the heart and aorta, and the results are applied to predicting the time course of the correlation between two time-separated A-scans derived from various regions of the liver. Such predictions are found to correspond well with data derived clinically, both from volunteers and from patients with liver metastases, using a commercial, real-time sector scanner. On the basis of Fourier spectral features of the clinically derived correlation patterns, a clear quantitative separation was demonstrated between the kinetic response of three classes of tissue: normal liver in volunteers, metastatic deposits in liver of cancer patients, and histologically normal liver regions in the same patients.
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The breasts of seven normal female volunteers were examined using a continuous wave, directional 10 MHz ultrasonic Doppler system. A range of quantitative features were extracted from recorded Doppler signals by first computing an average, single cardiac cycle sonogram from 4-6 overlayed cardiac cycles of sonogram data taken from each recording. Substantial variations were observed to occur in both frequency and amplitude characteristics of the Doppler signals during the menstrual cycle and pregnancy. For each subject the two breasts behaved similarly and the fluctuations correlated with known variations in blood hormone levels and breast surface temperature. In the one case of pregnancy, the mammary blood flow appeared to increase throughout pregnancy, beginning very shortly after conception. It is concluded that the normal fluctuations of the blood flow in the breast may make a large contribution to the variance of Doppler-derived blood flow features for the pre-menopausal breast. Use of the contralateral breast as a control is advocated for studies of the application of the Doppler method to the diagnosis and measurement of therapeutic response of breast cancer in young women. The usefulness of the contralateral breast as such a control might be enhanced by performing Doppler examinations only at about the midcycle. If the presence of a tumour were to alter these fluctuations there may be a possibility of using the effect to advantage alongside other methods for early diagnosis of breast cancer.
An approach to ultrasonic tissue characterization, using textural features of the B-scan image, is described. Portions of a B-scan image, 64 X 64 pixels spatially by 8 bits deep, are acquired from regions of interest and subjected to computer analysis. A systematic approach to defining a set of 93 textural features of a B-scan is described and methods and criteria for selecting optimum combinations of these are discussed. As a test of its power, the approach has been applied to the discrimination between the B-scan textures corresponding to livers and spleens of normal humans and various measures of "success" have been quantified both on a "training set only" and on a "training set plus test set" basis. The overall test probability of success of 82% on a single image and 94% on a subject yielding multiple images indicates the potential of the techniques for conditions where a subtle but uniform change in parenchymal texture may be present.
A method is described for quantifying tissue movement in vivo from the computation of correlation coefficient between pairs of A-scans with appropriate time separation. The method yields quantifiable and repeatable secondary patterns of soft tissue movement in response to primary cardiac movement in a given subject, shows consistently different results as between normal livers and a variety of abdominal tumours, and is sensitive to either progress or therapeutically-induced regression of malignant disease. While the results reported here have been obtained using somewhat simple and crude equipment, the method is well suited to implementation on a commercial real-time scanner.
This paper describes methods that have been developed for the accurate measurement of total and differential bulk acoustic scattering cross sections. Analysis is made of the sources of uncertainty entailed in measurements of this kind and a complete derivation is developed for the angular variation of the interrogated scattering volume. Experimentally determined values of differential scattering cross sections are reported for specimens of skeletal muscle, blood, liver, and secondary tumors arising in liver, obtained in the frequency range 4-7 MHz for scattering angles in the practically attainable range 60 degrees-150 degrees and also at 180 degrees (backscatter). A basis for extrapolating these results to other scattering angles can be derived from a combination of theoretical and experimental considerations, as presented in a companion paper [J. Acoust. Soc. Am. 79, 2048-2054 (1986)]. Based on such extrapolation, values for total scattering cross sections are estimated for the above tissues, the values are compared with determinations by different techniques as reported by other authors, and corresponding estimates are derived for the contribution of scattering processes to total attenuation in the tissues.
Theoretical formulations are developed, based on mathematical models of inhomogeneous continua for the expected angular variation of bulk scattering from human and animal tissues. These results are compared with experimental data on angular scattering from liver, muscle, and blood, reported in a companion paper [J. Acoust. Soc. Am. 79, 2034-2047 (1986)], and deductions are drawn as to the appropriateness of the various models for representing the mechanical structure of the different tissues. On this basis, the experimental data and theoretical formulations are used to derive estimates, appropriate to the frequency range of observation (4-7 MHz), of correlation distance (or effective scatterer spacing) d, the local variabilities of density and compressibility, gamma rho = delta rho/rho and gamma kappa = delta kappa/kappa 0, and their ratio gamma rho/gamma kappa. For blood, liver, and skeletal muscle, the values derived at 6 MHz for d are approximately 5, 55, and 75 microns and for gamma rho/gamma kappa are 0.5, 0.15, and 0.28, respectively. These results are, in particular, at variance with the commonly made assumption, based on evidence from low-frequency measurements, that the ratio gamma rho/gamma kappa is sufficiently small that density terms can be ignored in calculations of human tissue scattering.
Thirty-six pregnant women (ASA class I or II) at term who underwent general anesthesia and cesarean section received either ketamine, 1 mg/kg (n = 12); thiopental, 4 mg/kg (n = 13); or a combination of ketamine, 0.5 mg/kg, and thiopental, 2 mg/kg (n = 11). A blood pressure cuff inflated to 250 mm Hg isolated one arm from the effects of succinylcholine so that awareness during anesthesia could be assessed by asking the patient to move her hand. Although only one patient receiving ketamine responded to commands during anesthesia, 46% of patients receiving either thiopental or the combination responded to commands intraoperatively. No patient hallucinated, the incidence of dreams was low (11%), and no postoperative dysphoria was noted. Three patients (8%) had postoperative recall of intraoperative awareness; one had received thiopental and two the combination. Maternal intraoperative cardiovascular responses among the groups were similar, as were umbilical blood gas values, newborn Apgar scores, and neonatal neurobehavioral test scores at 4 and 24 hr. Ketamine more effectively blocked maternal responsiveness to commands and strong stimuli during the first few minutes after anesthetic induction for cesarean section than did thiopental or a combination of thiopental and ketamine, each at a lower dose.
Ultrasonic attenuation in fresh and 5% formalin fixed beef skeletal muscle has been measured, as a continuous function of frequency, in the range 1-8 MHz, for muscle fibre orientations both parallel and normal to the direction of propagation. Good agreement was found in all cases between two independent sets of measurements employing transmission and reflection techniques respectively. The data are consistent with a power law dependence of attenuation coefficient on frequency, with an exponent that is not significantly different from unity. For propagation normal to the fibres attenuation values are found as 1.1 +/- 0.15 and 1.6 +/- 0.15 dB cm-1 MHz-1 for fresh and fixed tissue respectively, the corresponding values for parallel propagation being 2.9 +/- 0.23 and 4.1 +/- 0.25 dB cm-1 MHz-1.