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We have developed a multiscale algorithm for elastic (or molded) alignment of images. There is a wide array of medical applications of elastic (as opposed to strictly rigid) alignment: Subtraction of previous images from current ones to identify changes is perhaps the most obvious. We present preliminary results of this molding technique on a variety of images, and conclude with some closing remarks about this and future directions and goals of this work.

We have developed a multiscale algorithm for elastic registration of images. Rigid registration has many applications but it is often limited by distortions in the images. For example, different views of the same object produce distortions. Common examples of slightly different views producing a distortion can be found in medical imaging, such as matching a current mammogram or chest radiograph with one from a previous year, and in remote sensing, such as matching images taken from different satellite positions. We have developed two methods of elastic registration. Both are multiscale but one used an iterative minimization of the local error and the other uses a windowed correlation. We present preliminary results of the elastic registration method used on windowed correlations.

We have introduced a new method of removing noise from images that identifies significant extrema and forces the pixel intensities between any two extrema to change monotonicly. The method has some similarities to wavelet denoising methods we worked with several years ago but is generally more stable and is effective on images with lower SNR's. In this paper the method of monotonic filtering is used to increase the sensitivity in functional magnetic resonance imaging (fMRI) studies. We have used the increased sensitivity to improve the temporal resolution in fMRI studies by roughly a factor of six. A motor activation study was acquired with single slice 256 x 256 pixel T2* weighted images; six cycles of finger tapping were acquired. Each cycle consisted of five images of rest followed by five images of right hand finger tapping followed by five images of left hand finger tapping. The z-scores were calculated and used as the activation map. The left and right activations were both clearly visible when all six cycles were used in the analysis. However, no definitive activation was seen for any one cycle. When the original 256 x 256 images were averaged down to 64 x 64 pixel images before calculation of the z-scores, the activations were partially identified. When the original images were filtered using the monotonic noise reduction algorithm, the left activation was clearly visible in three of the six cycles and partially visible in two others. The right activation was partially visible in 4 out of 6 cycles. Optimized noise reduction should improve the results significantly. The ability to use a single cycles is very important in fMRI studies because many stimuli are more difficult to maintain over many cycles and because complex processes such as in cognitive or memory activity do not have simple responses.

Many studies of monozygotic (MZ) twins have revealed evidence of genetic influences on intellectual functions and their derangement in certain neurologic and psychiatric diseases afflicting the forebrain. Relatively little is known about genetic influences on the size and shape of the human forebrain and its gross morphologic subdivisions. Using MRI and quantitative image analysis techniques, we examined neuroanatomic similarities in MZ twins and their relationship to head size and intelligence quotient (IQ). ANOVA were carried out using each measure as the dependent variable and genotype, birth order, and sex, separately, as between-subject factors. Pairwise correlations between measures were also computed. We found significant effects of genotype but not birth order for the following neuroanatomic measures: forebrain volume (raw, p < or = 0.0001; normalized by body weight, p = 0.0003); cortical surface area (raw, p = 0.002; normalized, p = 0.001); and callosal area (raw, p < or = 0.0001; normalized by forebrain volume, p = 0.02). We also found significant effects of genotype but not birth order for head circumference (raw, p = 0.0002; normalized, p < or = 0.0001) and full-scale IQ (p = 0.001). There were no significant sex effects except for raw head circumference (p = 0.03). Significant correlations were observed among forebrain volume, cortical surface area, and callosal area and between each brain measure and head circumference. There was no significant correlation between IQ and any brain measure or head circumference. These results indicate that: 1) forebrain volume, cortical surface area, and callosal area are similar in MZ twins; and 2) these brain measures are tightly correlated with one another and with head circumference but not with IQ in young, healthy adults.

The case records of four patients with scleroderma who booked for care between 1989 and 1994 at the Birmingham Women's Hospital (formerly the Birmingham Maternity Hospital), a tertiary care obstetric unit, were studied retrospectively. The aim of the study was to look at infertility, early and late pregnancy losses, fetal growth retardation and maternal complications in these four women afflicted with this rare condition. Two patients gave a history of infertility. There were two growth retarded fetuses and one intrauterine fetal death. Worsening Raynaud's phenomenon occurred in three patients. Another patient developed massive haematemesis due to an oesophageal tear resulting from intractable vomiting. Scleroderma may adversely affect pregnancy: obstetrical complications are common and require close monitoring.

Scores on five personality characteristics, extraversion, neuroticism, and psychoticism as well as reactive and proactive rebelliousness, and the appreciation of soft/nonrebellious and hard/rebellious rock-music videotapes were explored. After completing the personality tests, female and male undergraduates were exposed to rock-music videotapes and asked to rate various aspects of their enjoyment of each. Analysis indicated that psychoticism and reactive rebelliousness were associated with enjoyment in a parallel fashion. Specifically, respondents scoring high on psychoticism or high on reactive rebelliousness enjoyed hard/rebellious rock-music videotapes more than did their peers scoring low on psychoticism or low on reactive rebelliousness. The reverse was evident for the enjoyment of soft/nonrebellious rock-music videotapes. In contrast, scores on extraversion, neuroticism, and proactive rebelliousness were not associated with enjoyment. Gender differences emerged, however; women (n = 78) enjoyed soft/nonrebellious rock music more than did men (n = 60); and conversely, men enjoyed hard/rebellious rock music more than did women.

A modified steady-state free precession (SSFP) diffusion sequence is proposed for high resolution renal imaging. A pair of bipolar diffusion gradients was used to minimize the errors in measured apparent diffusion coefficient (ADC) caused by variations in T1, T2, and RF flip angle that have been observed with previously employed SSFP diffusion sequences. Motion sensitivity was reduced by the use of compensated gradients, frame-by-frame averaging, and a repetition time of 22 ms, which for a single-acquisition 128 x 128 image requires only 3 s. High resolution was achieved by signal averaging. The modified sequence was applied to in vivo diffusion measurements. In six normal rat kidneys the ADCs (mean +/- SD; x 10(-3) mm2/s) of the cortex, outer medulla, and inner medulla were 2.28 +/- 0.05, 2.38 +/- 0.10, and 2.95 +/- 0.05, respectively. The technique requires relatively large gradients to achieve adequate diffusion weighting.

Cholestasis of pregnancy is associated with increased fetal morbidity and mortality and should be treated actively. The significance attached to pruritus in pregnancy is often minimal, but it is a cardinal symptom of cholestasis of pregnancy, which may have no other clinical features. Eight women with previous cholestasis of pregnancy were referred to The Liver Unit within a 12 month period for advice concerning future pregnancies. Thirteen pregnancies had been affected by cholestasis of pregnancy and 12 had been treated expectantly with resultant perinatal morbidity or mortality in 11 (one normal delivery), including; eight stillbirths, two premature deliveries with fetal distress (one died in perinatal period), and an emergency caesarean section for fetal distress. The other pregnancy was treated actively and delivery was uncomplicated. Subsequently, three of these cases with recurrent cholestasis of pregnancy were referred while pregnant. In each, cholestasis developed with severe pruritus, gross increase of serum bile acids, and deranged liver tests. Each was treated with the choleretic agent ursodeoxycholic acid, with rapid clinical improvement and resolution of deranged biochemistry. In conclusion, cholestasis of pregnancy continues to be treated expectantly despite its association with increased morbidity and mortality and evidence suggesting improved prognosis with active treatment and the potential of reducing the associated perinatal mortality. In an uncontrolled series of three patients with cholestasis of pregnancy, ursodeoxycholic acid seemed to provide safe and effective therapy.

As tissue oxygen tension (pO2) is an important variable in cancer therapy, it would be of major clinical benefit to be able to measure pO2 noninvasively. Current methods for determining pO2 in clinical settings are limited to superficial tumors. The authors measured the apparent diffusion constant (ADC) in an implanted murine fibrosarcoma (RIF-1) using magnetic resonance imaging and correlated the ADC with tissue pO2 measured by electron paramagnetic resonance oximetry. The ADC correlates significantly with tissue pO2 in this tumor (r = 0.89; n = 14) and so may provide a noninvasive index of pO2 in tumors.

Principal components analysis (PCA) of images is important in many applications such as positron emission tomography and functional magnetic resonance imaging. PCA is difficult for image data because the correlation matrix is very large. We present a direct method of calculating the PCA of the voxels from the small matrix expressing the correlations between images, instead of the larger matrix representing the correlations between voxels. The method is fast and accurate. It is faster and requires less memory than a singular value decomposition, although it is less accurate. It is much faster and more accurate than iterative and other approximate methods developed for this problem.

We present two applications of wavelet and related techniques to problems arising in medical imaging. Both make considerable use of the edge detection and classification properties of wavelet-type representations. First we describe simple and effective techniques for image denoising and contrast enhancement based on the multiscale edge representation of images. These techniques are sufficiently flexible to successfully address the varying requirements posed by several different medical imaging modalities in common use today. Experimental results are presented to illustrate the application of these techniques to various types of medical images. Next we describe adapted waveform encoding, a technique for magnetic resonance imaging. One advantage of this technique is that it can be used to efficiently encode edge features of the object being imaged. This has a particular diagnostic application in tracking heart wall thickness during the cardiac cycle, which we present along with some experimental results along this line. We also present an analysis of the signal-to-noise ratios of images formed with this technique, as this is a factor of paramount importance in MRI. The fact that wavelet schemes tend to concentrate energy near edge features makes the result rather different than that found in standard Fourier based approaches. We indicate an exciting potential application of our technique: reducing spectral leakage in phosphorus spectroscopy.

Sulphation of oestrogens and monohydroxy bile acids is important in attenuating their cholestatic potential. Thus, impairment of sulphation could lead to retention of cholestatic compounds and precipitate intrahepatic cholestasis in susceptible individuals. We tested the hypothesis that such a mechanism may be involved in the pathogenesis of intrahepatic cholestasis of pregnancy. In vivo and in vitro assessment of sulphation capacity was performed in patients with cholestasis of pregnancy, compared with control females on and off the oestrogen-containing oral contraceptive pill and control individuals during normal pregnancy and post partum, to assess the influence of high oestrogen states upon this metabolic pathway. During in vivo studies utilising paracetamol as a metabolic probe, the proportion of paracetamol sulphate and sulphate: glucuronide ratio were decreased in those with elevated oestrogens, whether the rise in oestrogens was endogenous, in pregnancy (paracetamol sulphate p < 0.05; paracetamol sulphate:glucuronide ratio p < 0.01), or exogenous, with the contraceptive pill (paracetamol sulphate p = 0.2; paracetamol sulphate:glucuronide ratio p < 0.001). In vitro, platelet sulphotransferase activity was measured, utilising phenol as substrate. Sulphotransferase activity decreased during pregnancy compared with repeat measurements post partum (p < 0.005) and compared with non-pregnant individuals (p < 0.05). In conclusion, we have shown that elevated oestrogens are associated with significant impairment in sulphation capacity. An imbalance of sulphation with glucuronidation provoked by high circulating oestrogen levels may be contributory in the pathogenesis of cholestasis of pregnancy.

Wavelet transforms are multiresolution decompositions that can be used to analyze signals and images. They describe a signal by the power at each scale and position. Edges can be located very effectively in the wavelet transform domain. A spatially selective noise filtration technique based on the direct spatial correlation of the wavelet transform at several adjacent scales is introduced. A high correlation is used to infer that there is a significant feature at the position that should be passed through the filter. The authors have tested the technique on simulated signals, phantom images, and real MR images. It is found that the technique can reduce noise contents in signals and images by more than 80% while maintaining at least 80% of the value of the gradient at most edges. The authors did not observe any Gibbs' ringing or significant resolution loss on the filtered images. Artifacts that arose from the filtration are very small and local. The noise filtration technique is quite robust. There are many possible extensions of the technique. The authors see its applications in spatially dependent noise filtration, edge detection and enhancement, image restoration, and motion artifact removal. They have compared the performance of the technique to that of the Weiner filter and found it to be superior.

Wavelet encoding is presented and compared to phase encoding. In wavelet encoding a distribution of spins is excited by a slice selective RF pulse; for each repetition time the distribution excited has the profile of a wavelet at different scale and translation. The spin density can be reconstructed with an inverse wavelet transform. Wavelet encoding has three advantages over phase encoding: (1) there is no Gibb's ringing from partial volume effects, (2) the effective repetition time can be 36 times the repetition time for a 256 x 256 image, and (3) motion artifacts are local and dramatically reduced. Using wavelet encoding, a 256 x 256 T2-weighted projection image can be acquired in 33 s.

A new method of filtering MR images is presented that uses wavelet transforms instead of Fourier transforms. The new filtering method does not reduce the sharpness of edges. However, the new method does eliminate any small structures that are similar in size to the noise eliminated. There are many possible extensions of the filter.

Several groups have reported using a method of limiting the field of view (FOV) where the slices excited by the 90 and 180 degree pulses are perpendicular. However, only one slice can be excited during each repetition time, so multislice imaging is not possible. We present a modification of this method that allows multislice imaging. The slices excited by the 90 degrees and 180 degrees pulses are at a small angle; the field of view is limited and multislice imaging is possible. The modifications also allow the center of the FOV to be offset to any position. We describe the conditions that yield optimal images for the given FOV, slice thickness, and interslice gap. Representative images demonstrating the features of the technique are presented. The technique can be used to reduce the number of phase-encoding steps resulting in reduced imaging time, or it can be used to increase the spatial resolution without increasing the imaging time.

An attempt has been made to predict a difficult forceps delivery. The duration of the 7 to 10 cm cervical dilatation interval was measured from the completed cervimetric chart in 952 consecutive patients who delivered spontaneously between December 1973 and September 1974. The 7 to 10 cm cervical dilatation intervals of this group were compared with those of 378 consecutive patients in whom forceps were applied with the fetal head in the occipito-anterior position and 83 consecutive patients where Kielland's forceps rotation from the occipito-tranverse or occipito-posterior position was performed. The forceps deliveries were graded as 'easy', 'moderately difficult', or 'difficult'. In only 5% of the spontaneous delivery group did the 7 to 10 cm cervical dilatation interval exceed two hours. In the occipito-anterior and Kielland's forceps groups an 'easy' delivery could be expected if the 7 to 10 cm cervical dilatation interval was less than two hours. The greater this interval increased beyond two hours, the greater was the proportion of 'moderately difficult' and 'difficult' forceps deliveries.

Upper and lower limb blood flow was measured in 4 fullterm pregnant women in the left lateral and supine positions before and after epidural block. Radial artery mean blood pressure was recorded in 6 full term pregnant women under the same conditions. Before epidural block there was a much greater reduction in lower limb blood flow (39-1%) than in upper limb blood flow (13-5%) when women moved from the lateral to the supine position; this was probably the result of aortic compression. Mean radial artery pressure increased slightly by 4-6% due to maternal overcompensation in the upper part of the body. After epidural block, patients in the lateral position had a mean rise in lower limb blood flow of 25% and a reduction in upper limb blood flow of 37-2%. The mean arterial pressure remained unchanged. In the supine position there was no further reduction of upper limb blood flow; this was accompanied on average by a 9% fall in mean radial arterial pressure indicating decompensation in the mother. The leg blood flow fell less, 26-9% than before epidural block. In the supine position, a greater flow to the legs, associated with a decreased mean arterial pressure, would be expected to lead to a diminution in placental perfusion, which is the probable mechanism for foetal decompensation. Therefore the supine position should be avoided with an epidural block. In other patients it would be wise not to rely upon maternal compensatory mechanisms.

The clinical value of the 12-hour daily fetal movement count (DFMC) as a test of antepartum fetal wellbeing was assessed. The lowest 2-5% of 1654 DFMCs recorded by 61 women who subsequently delivered healthy infants fell below 10 movements per 12 hours. This level was taken as the lower limit of normal for clinical purposes. A normal DFMC in a population at risk was associated with a satisfactory fetal outcome. A low DFMC was associated with a high incidence of fetal asphyxia, and when fetal death occurred fetal movements rapidly diminished and stopped 12 to 48 hours before death. The DFMC is a generally applicable method of monitoring fetal welfare during pregnancy which provides an inexpensive adjunct or even an alternative to the more expensive placental function tests in current use.

The simultaneous multislice technique is a method of imaging multiple parallel slices with the number of echoes normally used to image a single slice. Images of 16 slices have been obtained from a single 128-echo acquisition. The distance between the slices can be decreased to approximately 15% of the field of view in the readout direction with the cost of significant image blurring. The image blurring is negligible when the distance between the slices approaches the field of view in the readout direction. The trade-offs are described, and equations and images are presented.

The possibility that Doppler ultrasound, as used in routine fetal monitoring by external cardiotocography, might stimulate fetal activity was investigated. A mean increase in fetal activity of over 90% was found, as judged by the fetal movement count.

A six-point scoring system for antenatal cardiotocography based upon baseline fetal heart rate (FHR) ad FHR response to fetal movements and Braxton-Hicks contractions has been described and tested in 89 patients. The 'six-point score' obtained within 24 hours of delivery or death of the fetus (D--1) was shown to be strongly associated both with the one-minute Apgar score and the nutritional status of the infant as reflected by centile birth weight. In 21 patients whose D--1 'six-point score' was 4 or less, analysis ofthe cardiologicographs performed on the previous day (D--2) showed that 14 infants already showed evidence of hypoxia. In the remaining seven patients, however, the previous day's six-point score had been normal (5 or 6); in six of these patients a persistently low daily fetal movement count or placental abruption led to repeat cardiotocography. Hypoxia affected the three components of the score in a progressive manner. Firstly there were alterations in the response of the FHR to Braxton-Hicks contractions followed by changes in the FHR response to fetal movements. Finally, fetal movements ceased and baseline FHR changes occurred mainly in the form of a trachycardia. The method of scoring was simple to use and could standardize reporting.

In pregnant patients at term the cardiovascular response to a Valsalva manoeuvre has been evaluated in the lateral and supine positions, before and after epidural block (T8-S5). There was no difference in the pattern of response under these four conditions. After epidural block, there was a tendency to a greater degree of hypotension and a slower recovery. In labour such repeated hypotension could account for the increase in fetal acidosis when the second stage of labour is conducted in the supine position.

Urinary protein excretion has been investigated using the iso-dalt technique in pregnant patients with hypertension and proteinuria, without hypertension but with proteinuria and without either hypertension or proteinuria. This high resolution electrophoretic technique has shown a great variation in the pattern of protein excreted by these patients, particularly those with hypertension. These showed an increased number of protein species in the urine, some of unknown identity. Two urines from this group appeared to contain no detectable albumin. Currently this technique is inappropriate for the routine analysis of urine proteins. However, further studies may determine the diagnostic value of these changes in urine excretion and allow the development of more specific assays.

Principal-components analysis is used to obtain a set of parameters for dual-energy radiography that completely describes the attenuation coefficient of any tissue over a given energy range. These parameters are the weighted averages of the densities of the elements present in a substance. Principal-components (PC) parameters are calculated for several soft tissues from measured attenuation coefficients published by Phelps et al. The calculated PC parameters are compared to the more conventional dual-energy representations of the attenuation coefficient: (1) the electron density/effective atomic number (or Compton/photoelectric) representation and (2) the equivalent water/equivalent aluminum thickness representation. The principal-components parameters represent the attenuation coefficients more accurately, and are more stable than the currently used parameters. In addition, these new parameters are sensitive to differences in the chemical composition and density, whereas the previous representations are primarily sensitive to changes in the density. It is concluded that the principal-components method provides a more sensitive and accurate indicator of changes in tissue composition than previous characterizations of the linear attenuation coefficient. The principal-components method provides a means for improving the accuracy of the characterization of tissues in dual-energy computed tomographic imaging and in dual-energy digital radiography.

Four serum biochemical fetoplacental function tests (HPL, unconjugated and total oestriol and AFP) were used to screen for intrauterine growth retardation in 793 patients attending an antenatal clinic. The birthweight corrected for sex, birth ranking and maternal size was used as an index of growth. The sensitivity and specificity of each test was calculated at varying cut-off points and plotted as 'Receiver Operator Curves'. HPL is clearly better than the oestriols or AFP with 80% sensitivity in detecting birth weights of less than the 5th centile when the 25th HPL centile is used as the cut-off point. However, the sensitivity of HPL is sufficiently low to make the value of screening questionable, particularly since 40% of all growth retarded infants were in mothers who did not attend antenatal clinic for screening and 25% of all growth retarded infants were detected by clinical examination.

Male subjects were placed into one of three intoxication conditions (no ethanol, low dose, high dose) and were exposed to humorous segments from television programs. During manifest intoxication or the corresponding period in the no-intoxication control condition, they were exposed, in a balanced order, to a segment containing blunt (i.e., unsophisticated, raw) humor and to a segment containing subtle (i.e., sophisticated, refined) humor. Subjects' facial reactions to the humorous stimuli were unobtrusively recorded and later analyzed by judges who were naive about the experimental conditions. Subjects also rated the funniness of the segments. The perceived funniness of blunt humor was found to increase with ethanol intoxication. For subtle humor, in contrast, perceived funniness was found to decrease with intoxication. This divergent interaction of reported humor appreciation was less apparent in the analysis of facial expressiveness. Although correlations between ratings and aspects of facial expression were generally positive, clearly corroborative support for the humor appraisals was found only in the frequency of smiles in response to subtle humor.

A comparison was made of the time of onset and duration of labour in 22 women taking digitalis and in 64 women who were not. Spontaneous labour occurred more than one week earlier and lasted about half as long in the patients taking digitalis. The likely explanation for this difference is that digitalis has a direct action on the myometrium.