Spectral CT of carotid atherosclerotic plaque: comparison with histology.

OBJECTIVE: To distinguish components of vulnerable atherosclerotic plaque by imaging their energy response using spectral CT and comparing images with histology. METHODS: After spectroscopic calibration using phantoms of plaque surrogates, excised human carotid atherosclerotic plaques were imaged using MARS CT using a photon-processing detector with a silicon sensor layer and microfocus X-ray tube (50 kVp, 0.5 mA) at 38-µm voxel size. The plaques were imaged, sectioned and re-imaged using four threshold energies: 10, 16, 22 and 28 keV; then sequentially stained with modified Von Kossa, Perl's Prussian blue and Oil-Red O, and photographed. Relative Hounsfield units across the energies were entered into a linear algebraic material decomposition model to identify the unknown plaque components. RESULTS: Lipid, calcium, iron and water-like components of plaque have distinguishable energy responses to X-ray, visible on spectral CT images. CT images of the plaque surface correlated very well with histological photographs. Calcium deposits (>1,000 µm) in plaque are larger than iron deposits (<100 µm), but could not be distinguished from each other within the same voxel using the energy range available. CONCLUSIONS: Spectral CT displays energy information in image form at high spatial resolution, enhancing the intrinsic contrast of lipid, calcium and iron within atheroma. KEY POINTS: Spectral computed tomography offers new insights into tissue characterisation. Components of vulnerable atherosclerotic plaque are spectrally distinct with intrinsic contrast. Spectral CT of excised atherosclerotic plaques can display iron, calcium and lipid. Calcium deposits are larger than iron deposits in atheroma. Spectral CT may help in the non-invasive detection of vulnerable plaques.

Spectroscopic (multi-energy) CT distinguishes iodine and barium contrast material in MICE.

OBJECTIVE: Spectral CT differs from dual-energy CT by using a conventional X-ray tube and a photon-counting detector. We wished to produce 3D spectroscopic images of mice that distinguished calcium, iodine and barium. METHODS: We developed a desktop spectral CT, dubbed MARS, based around the Medipix2 photon-counting energy-discriminating detector. The single conventional X-ray tube operated at constant voltage (75 kVp) and constant current (150 microA). We anaesthetised with ketamine six black mice (C57BL/6). We introduced iodinated contrast material and barium sulphate into the vascular system, alimentary tract and respiratory tract as we euthanised them. The mice were preserved in resin and imaged at four detector energy levels from 12 keV to 42 keV to include the K-edges of iodine (33.0 keV) and barium (37.4 keV). Principal component analysis was applied to reconstructed images to identify components with independent energy response, then displayed in 2D and 3D. RESULTS: Iodinated and barium contrast material was spectrally distinct from soft tissue and bone in all six mice. Calcium, iodine and barium were displayed as separate channels on 3D colour images at <55 microm isotropic voxels. CONCLUSION: Spectral CT distinguishes contrast agents with K-edges only 4 keV apart. Multi-contrast imaging and molecular CT are potential future applications.

Spectroscopic biomedical imaging with the Medipix2 detector.

This study confirms that the Medipix2 x-ray detector enables spectroscopic bio-medical plain radiography. We show that the detector has the potential to provide new, useful information beyond the limited spectroscopic information of modem dual-energy computed tomography (CT) scanners. Full spectroscopic 3D-imaging is likely to be the next major technological advance in computed tomography, moving the modality towards molecular imaging applications. This paper focuses on the enabling technology which allows spectroscopic data collection and why this information is useful. In this preliminary study we acquired the first spectroscopic images of human tissue and other biological samples obtained using the Medipix2 detector. The images presented here include the clear resolution of the 1.4mm long distal phalanx of a 20-week-old miscarried foetus, showing clear energy-dependent variations. The opportunities for further research using the forthcoming Medipix3 detector are discussed and a prototype spectroscopic CT scanner (MARS, Medipix All Resolution System) is briefly described.

Brain function and personality in normal males: a SPECT study using statistical parametric mapping.

Understanding the differences between individuals' personality types at a functional brain level is now possible due to recent developments in both functional brain imaging and personality models. The psychobiological model for temperament and character offers one approach to exploring personality. This study uses SPECT imaging to investigate brain function in relationship to the personality traits in the Temperament and Character Index. A general linear model approach was implemented at a voxel-by-voxel level, using quartile groupings for the personality predictors. t contrasts were used to investigate significant clusters of activation or deactivation. The results show a number of significant relationships between personality traits and regional cerebral blood flow, which show distinct nonlinear trends. All seven of the Cloninger personality traits were significantly related to regional cerebral blood flow. The results suggest that differences in brain function in some regions may reflect differences in personality traits.

The blanching process due to copper vapour laser treatment of port-wine stains.

We describe the causes and speed of transient blanching during copper vapour laser treatment of port-wine stains. Five watts of yellow (578 nm) light from a copper vapour laser was scanned over the lesion using a computer controlled scanning system. The clinical response of the lesion to treatment is transient blanching, followed immediately by erythema. The clinical response of sclerosed vessels is different in that an intravascular coagulum is observed. We measure the time taken for the lesion to blanch using two methods. First, high-speed photography is used to photograph the treatment process. Second, a photodiode measures the light re-emitted from the skin. Using illumination times of 3 to 5 ms and fluences of approximately 10 J cm-2, blanching times varied between 0 and 33 ms. We conclude that the cause of the transient blanching is not thermal denaturation of either collagen or epidermal melanin. Rather it is the rapid expulsion of red blood cells from the treated vessels. Our results have caused us to commence clinical trials using a new treatment protocol aimed at further improving the response of port-wine stains to copper vapour laser treatment.

High-resolution dosimetry using radiochromic film and a document scanner.

A method of reading exposed radiochromic film is described which has significant advantages over conventional densitometry. The method employs a document scanner and associated software for imaging the film. The resulting images are easily analysed using standard software to yield high-resolution dose maps. A calibration was performed which relates scanner signal to dose, allowing for the determination of dose at any point on an exposed film. Results obtained using a broad-band densitometer are compared to those where the scanner has been used. The technique was used to measure the dose distribution around a COMS-type ophthalmic applicator.

Modelling the distribution of laser light in port-wine stains with the Monte Carlo method.

Using the Monte Carlo method, we have calculated the distribution of absorbed light in skin during the laser treatment of port-wine stains. Our model includes the effect that the blood capillaries and epidermis have on the propagation of light through skin. It is more complete than those used by previous workers. In this paper, we change the number of scattering dimensions, the spot diameter, and the capillary separation and diameter, and we use the wavelengths 577 nm and 585 nm. One-dimensional scattering calculations are misleading but two-dimensional results suffice for large spot diameters. The model shows that changing the position or diameter of the capillaries has a larger effect on the distribution of absorbed light in the skin than changing the wavelength of the laser beam from 577 nm to 585 nm. Changing the wavelength does increase absorption in the deeper capillaries, but this is not significant. From our results, we discuss the optimal treatment of port-wine stains.

The facial distribution of port wine stains on patients presenting for laser treatment.

During a 2-year period, 232 patients with port wine stains presented for laser treatment. They were analyzed for the position of the port wine stain with respect to the right and left ophthalmic, maxillary, and mandibular divisions of cranial nerve V and the right and left cervical plexus. Fifty-one percent of the facial lesions were confined to either the right or left maxillary division, and 72% of the lesions were confined to just one of the eight nerve regions; 5.9% of the lesions occupied regions on both sides of the face, whereas 49.8% were confined to the right side and 44.3% to the left. In comparison with a group of 103 patients studied by Ohtsuka of Japan, there appeared to be significantly more patients in the maxillary division (p less than 0.0001) and significantly fewer patients in the ophthalmic division and in the combination of ophthalmic and maxillary divisions (p less than 0.00001).

A computer controlled scanner for the laser treatment of vascular lesions and hyperpigmentation.

A computer controlled scanner has been used with a copper vapour laser for the treatment of vascular lesions and hyperpigmented lesions. The computer controls the position and speed of travel of the laser spot during treatment. The illumination time is adjustable with a minimum of 1 ms. The light from the laser is scanned over the lesion so that the lesion is 'painted in' in a raster-like scan of arbitrary shape and produces a series of parallel lines 0.6 mm apart.

Copper vapour laser treatment of port-wine stains and other vascular malformations.

Over a 2-year period more than 1350 treatment sessions have been conducted with yellow 578 nm light from a copper vapour laser on a variety of vascular malformations. Of these sessions half were of port-wine stains, from 297 patients. The light is applied by scanning a 1 mm optical fibre approximately 2 mm above the lesion along the lines of Langer. We use a maximum scan rate of 3 s/cm2, which is the highest rate at which minimal blanching can be produced. Up to 6.5 watts of light has been used, and a typical energy fluence is 20 to 30 J/cm2. Topical melanin suppressing creams are used before and after treatment, in order to maximise the effectiveness of the treatment. Non-vasoconstricting anaesthetics are always used. Repeat treatments are 3 months apart. The scan rate we used was directly correlated with the light intensity. The degree to which the colour of the port-wine stains lightened after the first treatment was also well correlated with the scan rate (p less than 0.0005). The faster the scan rate, the greater the colour reduction. This provides some supporting evidence for the short illumination time that theoretical models have indicated as "ideal". The lightening was more marked for patients whose lesion colour was initially dark (p less than 0.0005). Those whose skin had a high melanin content (Maori, Polynesian and Asian) responded more slowly than others. Thirty-six patients have had a greater than 70% reduction in the size of their lesions after an average of four treatments. Ten patients have responded poorly after at least four treatments (10% of all those who have had four or more treatments). The occurrence of scarring, hyperpigmentation and hypopigmentation was low in comparison with that reported previously from the green light of argon ion lasers.

Computed temperature distributions around ectatic capillaries exposed to yellow (578 nm) laser light.

We have numerically modelled the thermal effects of yellow (577 or 578 nm) light illumination on the ectatic blood vessels of port wine stains. We investigated the effect of the laser treatment parameters of light irradiance and illumination time on the extent of coagulation (coagulation thickness) of the endothelial cells of the ectatic vessels. We assumed that this coagulation is dependent on heating the cells to a critical temperature (coagulation temperature). We iteratively adjusted the treatment parameters so that the model vessels had a maximum temperature that did not exceed the boiling point of blood. Given the likely range of variation of coagulation temperature, coagulation thickness and vessel size, coagulation temperature was found to have the greatest effect on the treatment parameters. Variations in coagulation thickness had less influence, and the diameter of the ectatic vessel (typically in the 30-80 microns diameter range) had the least effect. The treatment parameters that have been shown clinically to cause purpura (e.g. 6-7 cm-2 in 360 microseconds) were also studied. The purpura seen by some workers using pulsed dye lasers is most likely to be the result of vaporisation of blood leading to the rupture of the vessel. We conclude that, in order to achieve coagulation with these short laser pulses, the choice of irradiance is critical.

Histology of port wine stains after copper vapour laser treatment.

We report histological changes in four patients with port wine stains treated with 578 nm yellow light from a high power copper vapour laser. Histology showed that selective damage occurred to the ectatic blood-vessels in the dermis, without haemorrhage and damage to non-vascular structures, and without scarring. The initial damage to the overlying epidermis was not permanent, and the damaged ectatic vessels returned to normal size or were completely necrosed and replaced by collagen.

Thermal profiles of blood vessels heated by a laser.

Thermal profiles of ectatic capillaries, modelled on those found in port wine stain birthmarks, are calculated by a method of finite differences. Yellow 578nm light is assumed to illuminate these vessels. The coagulation of endothelial cells is assumed to occur when the cells are heated to at least 70 degrees C. We model this by asking that a point 6 microns above the top of the vessel lumen attains a temperature of 70 degrees C. We constrain the parameters to prevent heating of blood above 100 degrees C, so as to avoid vapourisation. The treatment parameters of dose and illumination time are varied until they produce thermal profiles that show the model's coagulation conditions. being treated and are rather longer than the thermal relaxation time of the vessel and also much longer than the pulses of pulsed dye lasers.

Effects of occipital lobectomy upon eye movements in primate.

1. Eye movements were recorded before and after bilateral occipital lobectomy in six rhesus monkeys trained to fixate and to follow small targets. Striate cortex was completely removed in two animals; small islands islands remained in the others. In all animals portions of extrastriate cortex were also removed but the medial superior temporal area in the superior temporal sulcus was largely spared. Optokinetic nystagmus (OKN) was markedly altered but not abolished in all animals. The immediate pursuit component of OKN was eliminated leading to a poor response to stimuli comprised of high frequencies. The velocity-storage component of OKN was present, but the maximum value of OKN that could be achieved was decreased to 6 and 16 degrees/s in the two most severely affected animals (preop, 65-116 degrees/s). The residual OKN was similar to that of afoveate animals with a diminished response to high velocities of retinal-image motion and a temporal to nasal predominance during monocular viewing. 2. In the initial postoperative period all animals appeared completely blind. Within 1-6 mo, however, they regained an ability to make visually guided saccades to, and smooth pursuit of, small targets. Saccades were nearly as accurate as preoperatively, but saccade amplitudes were more variable and saccade latencies increased. In the two animals with a complete removal of striate cortex, gains (eye velocity/target velocity) of smooth pursuit during sinusoidal tracking (60 degrees/s, 0.5 Hz) were 0.9 and 0.95. During tracking of step-ramp (Rashbass) stimuli with 60 degrees/s ramps, the average acceleration of the eyes during the first 120 ms of smooth pursuit was 189-278 degrees.s-1.s-1 (preop range, 154-418 degrees.s-1.s-1). In other respects, though, smooth pursuit was not normal. Latencies were increased two- to threefold, and tracking was more variable. 3. Paradoxically, as visually guided saccades and pursuit recovered, some other ocular motor functions deteriorated. Spontaneous and gaze-evoked nystagmus developed 3-6 mo after occipital lobectomy; the time constant of the neural eye-position integrator dropped to values as low as 2.6-4.8 s. The maximum slow-phase velocity of OKN also decreased. 4. The findings immediately after occipital lobectomy indicate that in normal primates occipital cortex is necessary for visually guided saccades and smooth pursuit as well as for the immediate component of OKN. Occipital cortex also makes the predominant contribution toward the generation of the velocity-storage component of OKN.(ABSTRACT TRUNCATED AT 400 WORDS)