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Biomedical subjects

C R Hill

Publications and source records attributed to C R Hill.

At least 19 recordsLinked to original sources
PubMed1999

Histological study of normal and tumor-bearing liver treated with focused ultrasound.

The purpose of this investigation was to study the tissue damage (including blood vessels) on both normal and tumor-bearing experimental livers and the course of liver repair after focused ultrasound (FUS) treatment using histological evaluation. A series of experiments were carried out in vivo. Tissue was treated using arrays of ultrasound exposures with a frequency of 1.7 MHz, in situ spatially averaged focal intensity (I(SAL) in situ) of 212-266 W/cm2 (corresponding to in situ spatial peak intensity of 382-479 W/cm2), 5-10 s exposure duration and 1.5-3.0 mm exposure separation. Tissue specimens were examined using both light and electron microscopy. The damage to the blood vessel walls was studied. The results showed the existence of indirect tissue damage in both normal and tumor tissue that is outside of the treatment volume, due to disruption of the major blood vessels supplying the adjacent area. Evidence for liver regeneration was found 2 months after FUS treatment.

Animals↗
PubMed1998

Treatment of implanted liver tumors with focused ultrasound.

This article reports treatment of implanted liver tumors (HSN fibrosarcoma) with focused ultrasound (FUS). Experiments were carried out on implanted liver tumors in vivo. In order to determine the optimum treatment conditions, various combinations of exposure parameters were investigated. The results showed that it is possible to achieve total destruction of tumor cells in the treatment volume using an FUS system with a frequency of 1.7 MHz, with in situ ISAL of 261 W/cm2, 5-s exposure duration, and 1.5-mm exposure separation, with an in situ ISAL of 266 W/cm2, 10-s duration, and 2-mm separation, or with in situ ISAL of 213 W/cm2, 8-s duration, and 1.5-mm separation. Fifteen selected tumors were treated with these experimentally determined "optimum" exposure conditions. All the tumors were destroyed completely. Assessment of tumor viability in the treated volume was performed using both histologic and tissue culture methods. The mechanism of tumor damage, the limitations of the tumor model, and the effect of exposure parameters and liver blood flow on the treatment are discussed.

Animals↗
PubMed1998

A comparison of T2 and gadolinium enhanced MRI with CT myelography in cervical radiculopathy.

Two MRI strategies which have been reported to be effective in assessing cervical exit foramina, were prospectively compared with CT myelography in 20 patients with cervical radiculopathy. The first strategy utilized 3D T2* images, the second gadolinium enhanced 2D T1 images. Gadolinium (dimeglumine gadopentetate, Schering Ltd) enhanced images did not confer any benefit in the investigation of this condition, probably due to enhancement of herniated disc material and osteophytes adjacent to the neurocentral joint. Three-dimensional (3D) T2* white cerebrospinal fluid images had an accuracy approaching 90% for the diagnosis of foraminal encroachment, compared with a gold standard. MRI including a 3D T2* sequence is thus an acceptable primary investigation for cervical radiculopathy, but when the findings are incompatible with clinical symptomatology, CT myelography is still indicated.

Adult↗
PubMed1997

Influence of ablated tissue on the formation of high-intensity focused ultrasound lesions.

In order to ablate tumours using high-intensity focused ultrasound (HIFU) it is necessary to irradiate the tumour with a confluent array of single ultrasound exposures. We have identified a phenomenon that we term lesion-to-lesion interaction, which occurs when the spatial separation of individual exposures is such that an existing lesions appears to affect the formation of a subsequent lesion. This article investigates the implications of this phenomenon for strategies to ablate large tissue volumes in the treatment of hepatic metastases. Experiments on pig and rat livers have been carried out using a focused ultrasound system with a frequency of 1.7 MHz, an in situ spatially averaged focal intensity (ISAL) of 133-658 W cm-2 (ISP of 239-1185 W cm-2) and an exposure duration of 5-15 s. The results show that there is interaction between lesions that spatial exposure separations that depend on the intensities and exposure durations used. As a result, either subsequent lesions form closer to the ultrasound source (if the focal peak of the ultrasound beam is placed deep inside the liver tissue) or their length is reduced (if the focal peak is near the liver surface). An explanation is suggested for this effect and a strategy for its avoidance during in vivo HIFU treatment is discussed.

Animals↗
PubMed1995

Lumbosacral skin markers and identification of occult spinal dysraphism in neonates.

Some skin lesions over the spine are known to be associated with occult spinal dysraphism, but the significance of common skin lesions, such as sacral pits and dimples, is uncertain. In this prospective study, 95 neonates (1.9% of 4989 live births) were referred with possible markers of occult spinal dysraphism. Seven of 94 babies examined had abnormalities demonstrated by spinal ultrasound, compared with 5 of 105 controls. In 2 of 94 and 3 of 105 of these, the conus medullaris was located at L3 but no other abnormalities were found. Of the 75 babies with a sacral dimple or pit alone, none had an abnormality, suggesting that these skin lesions do not indicate a high risk of occult spinal dysraphism.

Biomarkers↗
PubMed1995

Review article: high intensity focused ultrasound--potential for cancer treatment.

The prospect of being able to use "minimally invasive" surgical techniques is of great interest today, particularly for reasons of health economics, patient acceptability and reduced morbidity. High intensity focused ultrasound (HIFU) has long been known to offer the potential of very precise "trackless lesioning" but has only recently, with the advent of high quality methods of medical imaging, become a practicable possibility. High intensity beams can readily be achieved using either bowel or lens focusing procedures and, by choice of a suitable acoustic frequency, regions of tissue destruction--"lesions"--can be induced at depths of up to at least 10 cm with exposure times of the order of 1 s. Theoretical and experimental evidence indicates that the primary mechanism of damage is thermal, i.e. "cooking" of the tissues. Both conventional cavitation and boiling of tissue water may complicate the situation. Furthermore, substantial non-linear behaviour is involved. On histological appearance the lesions have a spatially sharp demarcation between regions of normal and dead cells. When attempts are made to ablate a block of tissue, by creating an array of adjacent elementary lesions, a phenomenon is observed of inhibition of formation of a lesion whose placing is too close to that of a neighbour. Provided that this problem is dealt with, complete ablation of an extended block of tissue can be achieved. For animal tumours in particular, this observation is reinforced by evidence both of in vitro cell survival and of tumour growth delay experiments. Clinically, the sites accessible for HIFU treatment will be limited by the need for a suitably wide acoustic window that either is available naturally or can be provided by a relatively minor surgical procedure. Tumour sites which thus offer a realistic prospect for local control (and some of which are already the subject of phase 1 trials) include liver, bladder, kidney, prostate, breast and brain. There is also considerable interest in non-cancer applications in these and other sites.

Humans↗
PubMed1994

Lesion development in focused ultrasound surgery: a general model.

An analytical model has been constructed for the process of formation of thermal lesions in tissue, resulting from exposure to intense, highly focused ultrasound beams such as may be used in minimally invasive surgery. The model assumes a Gaussian approximation to beam shape in the focal region and predicts, for any such focal beam, the time delay to initiation of a lesion and the subsequent time course of growth of that lesion in lateral and axial dimensions, taking into account the effects of thermal diffusion and blood perfusion. The necessary approximations and assumptions of the model are considered. Comparison of predictions with experimentally measured data on excised pig liver indicate generally good agreement. Comparisons are also made of this theory with previously published data on exposure-time dependence of lesioning threshold intensity. Deficiencies are identified in existing practice for measuring and reporting acoustic exposures for focused ultrasound surgery, and the proposal is therefore made that a quantity that would be more satisfactory, from the viewpoints both of metrology and biophysical relevance, is the intensity spatially averaged over the area enclosed by the half-pressure-maximum contour in the focal plane, as determined under linear conditions, provisionally denoted as ISAL.

Acoustics↗
PubMed1994

Optimum acoustic frequency for focused ultrasound surgery.

A model is described that enables calculation of ultrasound lesioning rate (inverse of time to achieve a threshold lesion in the absence of thermal redistribution) as a function of acoustic frequency, tissue penetration depth, d, attenuation coefficient at specific frequency, mu, and power of dependence of attenuation on frequency, n. Two acoustic power conditions are considered: unlimited power, and power limited by the material properties of the transducer and the constraint that its dimensions be scaled to tissue penetration depth. Optimum frequencies for these two conditions are found to be, respectively, [(2 + n)/n mu d]1/n and [(3 - n)/n mu d]1/n. The tissue path attenuation, for both conditions, is independent of frequency, with a value of approximately 10 dB. Values of predicted lesioning rates under optimum frequency conditions are presented, and the likely constraints imposed by cavitation and propagation nonlinearity are considered.

Acoustics↗
PubMed1994

Minimally invasive cancer surgery using focused ultrasound: a pre-clinical, normal tissue study.

Using a focused 1.7 MHz ultrasound field (focal length/transducer diameter ratio of 1.7) and in situ intensities spatially averaged within the half-pressure maximum contour in the range 100-400 W cm-2, ablative lesions have been prescriptively placed singly and in arrays, in the livers and bladder walls of adult female Large White pigs. Exposures were made through the skin with up to 8 cm of intervening tissue. Ablative lesions were placed under ultrasonic guidance, and specific lesion echoes were subsequently observed in two cases. Animals were sacrificed immediately after induction of ultrasonic lesions, post-mortems were performed, as were histological examinations of normal and damaged tissue. There was clear demarcation between ablated and normal tissue. Provided that simple rules on exposure technique had been observed, there was no evidence of inadvertent tissue damage, either locally to the treatment site, or in the tissue lying between the source and the target. This study is a useful step in demonstrating the feasibility of clinical trials for the use of this technique in treating bladder tumours and solitary liver metastases.

Animals↗
PubMed1993

Histological changes in rat liver tumours treated with high-intensity focused ultrasound.

This paper reports the histological changes found in rat liver tumours treated with high-intensity focused ultrasound. HSN fibrosarcoma, implanted subcapsularly in the livers of CBH rats, were treated using an array of ultrasound exposures. At predetermined times following treatment, the rats were sacrificed and tissue specimens were examined histologically. Evident tissue damage was confined to regions that had been given high ultrasound exposures. Within these regions ("lesions") there was no evidence of intact cells whereas in the sharply demarcated surrounding tissue there was no evidence of cell damage. Where individual ultrasound lesions had been placed in sufficiently close proximity, there was correspondingly continuous and complete cell destruction. There is suggestive evidence that tissue damage may arise through two different mechanisms: direct, primarily thermal, damage and indirect damage resulting from compromised blood supply. Under the same exposure conditions, normal liver cells appear to lose their morphological structure more readily than do tumour cells.

Animals↗
PubMed1993

Effect of blood perfusion on the ablation of liver parenchyma with high-intensity focused ultrasound.

This paper discusses the effect of blood perfusion on the ablation of rat liver tissue with high-intensity focused ultrasound (HIFU). For this study a practical method has been developed, in which the liver blood flow can be reduced by ligation of the hepatic artery and portal vein. During the treatment the rat liver was mobilized out of the abdomen and the blood flow was measured using both the radioactive microsphere method and a laser Doppler blood-flow monitor. The results show that the hepatic blood flow was about 23 ml/100 g min-1 via the hepatic artery and about 227 ml/100 g min-1 via the portal vein. The total liver blood flow was reduced by 98% when both the hepatic artery and portal vein were ligated. Comparative lesions were made on the same liver lobes of rats with both normal and reduced blood flow using a focused ultrasound beam of 1.7 MHz, 67-425 W cm-2 spatially averaged focal intensity ISAL and 2-20 s exposure duration. A marked difference has been found between the lesion dimensions obtained with normal blood flow and that with reduced blood flow. For exposures at 169 W cm-2 the lesion diameter with normal blood flow was reduced by 14% for 3 s exposure duration compared to that obtained with both hepatic artery and portal vein ligated, while the reduction was more than 20% for longer durations.

Animals↗
PubMed1991

What might echography learn from image science?

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.

Humans↗
PubMed1990

Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus.

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:

Age Factors↗