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1.
Neuroimage Clin ; 23: 101880, 2019.
Article in English | MEDLINE | ID: mdl-31200150

ABSTRACT

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes.


Subject(s)
Chronic Pain/pathology , Chronic Pain/physiopathology , Diffusion Tensor Imaging , Evoked Potentials, Motor/physiology , Motor Cortex/physiopathology , Motor Disorders/physiopathology , Neuralgia/pathology , Neuralgia/physiopathology , Radiculopathy/pathology , Radiculopathy/physiopathology , Aged , Chronic Pain/diagnostic imaging , Electromyography , Female , Humans , Low Back Pain/diagnostic imaging , Low Back Pain/pathology , Low Back Pain/physiopathology , Lumbar Vertebrae , Male , Middle Aged , Neuralgia/diagnostic imaging , Radiculopathy/diagnostic imaging , Transcranial Magnetic Stimulation
2.
Eur J Pain ; 2018 Apr 28.
Article in English | MEDLINE | ID: mdl-29704875

ABSTRACT

BACKGROUND: Transcranial direct-current stimulation (tDCS) applied over the primary motor cortex has been shown to be effective in the treatment of a number of chronic pain conditions. However, there is a lack of understanding of the top-down analgesic mechanisms involved. METHOD: In this study, we investigated the effects of tDCS on the facilitation of subjective sensory and pain scores using a transcutaneous electrically evoked measure of temporal summation. In this randomized, blinded, cross-over study healthy subjects received a single stimulus given at 0.9× pain threshold (pTh) over the L5 dermatome on the lateral aspect of the right leg, followed by a train of 5 stimuli given at 0.5, 1, 5 and 20 Hz before and after 20 min of sham or anodal tDCS (2 mA) applied over the primary motor cortex. Ratings of sensation and pain intensity were scored on a visual analogue scale (VAS). RESULTS: Temporal summation leading to pain only occurred at higher frequencies (5 and 20 Hz). Sham or real tDCS had no effect over temporal summation evoked at 5 Hz; however, there was a significant analgesic effect at 20 Hz. Sham or real tDCS had no effect over acute, single stimuli-evoked responses. CONCLUSION: These results indicate that anodal tDCS applied to the primary motor cortex preferentially modulates temporal summation induced by high-frequency electrical stimulation-induced pain. The inhibitory effects of tDCS appear to be dynamic and dependent on the degree of spinal cord excitability and may explain the higher analgesic efficacy in patients with moderate to severe chronic pain symptoms. SIGNIFICANCE: The analgesic effects of tDCS are dependent on spinal cord excitability. This work provides insight into top-down modulation during acute pain and temporal summation. This knowledge may explain why tDCS has a higher analgesic efficacy in chronic pain patients.

3.
Pain ; 154(9): 1680-1690, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23707289

ABSTRACT

Pontospinal noradrenergic neurons form part of an endogenous analgesic system that suppresses acute pain, but there is conflicting evidence about its role in neuropathic pain. We investigated the chronology of descending noradrenergic control during the development of a neuropathic pain phenotype in rats following tibial nerve transection (TNT). A lumbar intrathecal cannula was implanted at the time of nerve injury allowing administration of selective α-adrenoceptor (α-AR) antagonists to sequentially assay their effects upon the expression of allodynia and hyperalgesia. Following TNT animals progressively developed mechanical and cold allodynia (by day 10) and subsequently heat hypersensitivity (day 17). Blockade of α2-AR with intrathecal yohimbine (30 µg) revealed earlier ipsilateral sensitization of all modalities while prazosin (30 µg, α1-AR) was without effect. Established allodynia (by day 21) was partly reversed by the re-uptake inhibitor reboxetine (5 µg, i.t.) but yohimbine no longer had any sensitising effect. This loss of effect coincided with a reduction in the descending noradrenergic innervation of the ipsilateral lumbar dorsal horn. Yohimbine reversibly unmasked contralateral hindlimb allodynia and hyperalgesia of all modalities and increased dorsal horn c-fos expression to an innocuous brush stimulus. Contralateral thermal hyperalgesia was also reversibly uncovered by yohimbine administration in a contact heat ramp paradigm in anaesthetised TNT rats. Following TNT there is an engagement of inhibitory α2-AR-mediated noradrenergic tone which completely masks contralateral and transiently suppresses the development of ipsilateral sensitization. This endogenous analgesic system plays a key role in shaping the spatial and temporal expression of the neuropathic pain phenotype after nerve injury.


Subject(s)
Neuralgia/etiology , Neuralgia/therapy , Pons/metabolism , Spinal Cord/metabolism , Tibial Neuropathy/complications , Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Adrenergic alpha-2 Receptor Antagonists/therapeutic use , Analysis of Variance , Animals , Disease Models, Animal , Dopamine beta-Hydroxylase/metabolism , Electromyography , Functional Laterality , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Male , Neuralgia/complications , Pain Measurement , Pain Threshold/drug effects , Pons/drug effects , Prazosin/therapeutic use , Rats , Rats, Wistar , Spinal Cord/drug effects , Time Factors , Yohimbine/therapeutic use
4.
Phys Med Biol ; 53(15): 4123-35, 2008 Aug 07.
Article in English | MEDLINE | ID: mdl-18612178

ABSTRACT

The ability to quantify and qualify the progression of joint degeneration is becoming increasingly important in surgery. This paper examines the patterns of relative ultrasound reflection from normal, artificially and naturally degraded cartilage-on-bone, particularly investigating the potential of the ratio of reflection coefficients from the surface and osteochondral junction in distinguishing normal from osteoarthritic tissue. To this end, the reflection coefficients from the articular surface and osteochondral junction of normal cartilage-on-bone samples were calculated and compared to samples after the removal of proteoglycans, disruption of the collagen meshwork, delipidization of the articular surface and mechanical abrasion. Our results show that the large variation across normal and degraded joint samples negates the use of an isolated bone reflection measurement and to a lesser extent, an isolated surface reflection. The relative surface to bone reflections, calculated as a ratio of reflection coefficients, provided a more consistent and statistically significant (p < 0.001) method for distinguishing each type of degradation, especially osteoarthritic degradation, and due to the complementary relationship between surface and bone reflections was found to be an effective method for distinguishing degraded from normal tissue in the osteoarthritic joint, independent of the site of initiation of the osteoarthritic process.


Subject(s)
Cartilage/diagnostic imaging , Cartilage/metabolism , Joints/diagnostic imaging , Joints/metabolism , Cartilage/cytology , Cartilage/pathology , Cartilage, Articular/cytology , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Humans , Joints/cytology , Joints/pathology , Osteoarthritis/diagnostic imaging , Osteoarthritis/metabolism , Osteoarthritis/pathology , Surface Properties , Ultrasonography
5.
Neuroscience ; 141(2): 621-636, 2006 Aug 25.
Article in English | MEDLINE | ID: mdl-16777348

ABSTRACT

The slow (<1 Hz) rhythm is an electroencephalogram hallmark of resting sleep. In thalamocortical neurons this rhythm correlates with a slow (<1 Hz) oscillation comprising recurring UP and DOWN membrane potential states. Recently, we showed that metabotropic glutamate receptor activation brings about an intrinsic slow oscillation in thalamocortical neurons of the cat dorsal lateral geniculate nucleus in vitro which is identical to that observed in vivo. The aim of this study was to further assess the properties of this oscillation and compare them with those observed in thalamocortical neurons of three other thalamic nuclei in the cat (ventrobasal complex, medial geniculate body; ventral lateral nucleus) and two thalamic nuclei in rats and mice (lateral geniculate nucleus and ventrobasal complex). Slow oscillations were evident in all of these additional structures and shared several basic properties including, i) the stereotypical, rhythmic alternation between distinct UP and DOWN states with the UP state always commencing with a low-threshold Ca2+ potential, and ii) an inverse relationship between frequency and injected current so that slow oscillations always increase in frequency with hyperpolarization, often culminating in delta (delta) activity at approximately 1-4 Hz. However, beyond these common properties there were important differences in expression between different nuclei. Most notably, 44% of slow oscillations in the cat lateral geniculate nucleus possessed UP states that comprised sustained tonic firing and/or high-threshold bursting. In contrast, slow oscillations in cat ventrobasal complex, medial geniculate body and ventral lateral nucleus thalamocortical neurons exhibited such UP states in only 16%, 11% and 10% of cases, respectively, whereas slow oscillations in the lateral geniculate nucleus and ventrobasal complex of rats and mice did so in <12% of cases. Thus, the slow oscillation is a common feature of thalamocortical neurons that displays clear species- and nuclei-related differences. The potential functional significance of these results is discussed.


Subject(s)
Cerebral Cortex/cytology , Neurons/physiology , Periodicity , Sleep Stages/physiology , Thalamic Nuclei/cytology , Action Potentials/drug effects , Action Potentials/physiology , Action Potentials/radiation effects , Animals , Benzoates/pharmacology , Cats , Cycloleucine/analogs & derivatives , Cycloleucine/pharmacology , Dose-Response Relationship, Radiation , Electric Stimulation/methods , Excitatory Amino Acid Antagonists/pharmacology , Glycine/analogs & derivatives , Glycine/pharmacology , In Vitro Techniques , Mice , Mice, Inbred C57BL , Neurons/drug effects , Neurons/radiation effects , Rats , Rats, Wistar , Species Specificity
6.
Neuroscience ; 110(3): 395-401, 2002.
Article in English | MEDLINE | ID: mdl-11906781

ABSTRACT

Spikelets, or fast prepotentials as they are frequently referred to, are a common feature of the electrophysiology of central neurones and are invariably correlated with the presence of electrotonic coupling via gap junctions. Here we report that in the presence of the metabotropic glutamate receptor agonists, trans-ACPD or DHPG, thalamocortical neurones of the cat dorsal lateral geniculate nucleus maintained in vitro exhibit stereotypical spikelets that possess similar properties to those described in other brain areas. These spikelets were routinely observed in the presence of antagonists of fast chemical synaptic transmission, were resistant to the application of a variety of voltage-dependent Ca(2+) channel blockers but were abolished by tetrodotoxin. In addition, spikelets were reversibly blocked by the putative gap junction blocker carbenoxolone and were nearly always accompanied by dye-coupling. These results indicate that thalamocortical neurones may be electrotonically coupled via gap junctions with spikelets representing attenuated action potentials from adjoining cells. We suggest that the presence of electrotonic communication between thalamocortical neurones would have major implications for the understanding of both physiological (Steriade et al., 1993; Sillito et al., 1994; Alonso et al., 1996; Neuenschwander and Singer, 1996; Weliky and Katz, 1999) and pathological (Steriade and Contreras, 1995; Pinault et al., 1998) synchronised electrical activity in the thalamus.


Subject(s)
Action Potentials/physiology , Cell Communication/physiology , Gap Junctions/physiology , Geniculate Bodies/physiology , Neurons/physiology , Synaptic Transmission/physiology , Visual Cortex/physiology , Visual Pathways/physiology , Action Potentials/drug effects , Animals , Anti-Ulcer Agents/pharmacology , Calcium Channel Blockers/pharmacology , Carbenoxolone/pharmacology , Cats , Cell Communication/drug effects , Electric Stimulation , Excitatory Amino Acid Antagonists/pharmacology , GABA Antagonists/pharmacology , Gap Junctions/drug effects , Geniculate Bodies/cytology , Geniculate Bodies/drug effects , In Vitro Techniques , Neurons/cytology , Neurons/drug effects , Sodium Channel Blockers/pharmacology , Synaptic Transmission/drug effects , Visual Cortex/cytology , Visual Cortex/drug effects , Visual Pathways/cytology , Visual Pathways/drug effects
7.
Ultrasound Obstet Gynecol ; 16(2): 154-8, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11117086

ABSTRACT

OBJECTIVE: To establish reference intervals for fetal lung growth. DESIGN: Longitudinal observational study. SUBJECTS: Fifty-eight women with initially uncomplicated singleton pregnancies were recruited from the antenatal population of a teaching hospital. Four women were excluded from the final analysis because of complications arising in their pregnancy. METHODS: Each subject was serially scanned at monthly intervals. At each visit lung volume was measured using an ultrasound-based computerized three-dimensional imaging system. Multilevel models were used to determine conditional and unconditional reference intervals. RESULTS: Reference intervals for fetal lung growth were derived. Fetal lung volume increases in a non-linear way with gestation. CONCLUSIONS: Our computerized system has the capacity to be used in conjunction with any standard two-dimensional ultrasound scanner in order to measure volume. Lung volume measurement may be useful in predicting pulmonary hypoplasia.


Subject(s)
Lung/diagnostic imaging , Lung/embryology , Ultrasonography, Prenatal/methods , Adult , Embryonic and Fetal Development , Female , Gestational Age , Humans , Longitudinal Studies , Mass Screening/methods , Pregnancy , Sensitivity and Specificity , Ultrasonography, Doppler/methods
8.
Neuropharmacology ; 38(11): 1699-706, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10587086

ABSTRACT

Cortical and thalamic neurones play a major role in the generation/expression of spike and wave discharges (SWDs), the main electroencephalographic (EEG) feature of absence seizures. The detailed mechanisms leading to this paroxysmal EEG activity, however, are still poorly understood. We have now made in vivo intracellular recordings from layer V cortical neurones of the facial motor cortex and from thalamocortical (TC) neurones of the ventroposteromedial and ventroposterolateral nuclei in a well established model of this disease: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The main feature of the intracellularly recorded activity of TC neurones during spontaneous SWDs was the presence of rhythmic sequences of synaptic potentials consisting of an EPSP closely followed by 2-6 IPSPs. These rhythmic sequences were superimposed on a small tonic hyperpolarization that lasted for the whole duration of the SWD and was still present at potentials close to -85 mV. The rhythmic IPSPs, on the other hand, had a reversal potential of -68 mV, and always appeared as depolarizing events when recording with KCl-filled electrodes at -55 mV. Low frequency electrical stimulation of the corresponding cortical area evoked in TC neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. The main feature of the intracellular activity recorded in cortical neurones during spontaneous SWDs was the presence of rhythmic depolarizations. Their frequency was similar to the one of SWDs in the EEG, and was not affected by DC injection. The amplitude of the rhythmic depolarizations, however, increased following steady hyperpolarization of the neurone by DC injection. An increase in the apparent input resistance of cortical neurones was observed during SWDs compared to the inter-SWDs periods. Low frequency electrical stimulation of the contralateral striatum evoked in cortical neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. Our data indicate that there are no rhythmic GABA(B) IPSPs and low threshold Ca2+ potentials in GAERS TC neurones during SWDs, but rhythmic sequences of EPSP/IPSPs superimposed on a tonic hyperpolarization that might represent a long lasting GABA(B) IPSP. Further experiments are required to clarify the nature of the voltage waveform and the increase in input resistance observed in cortical neurones during spontaneous SWDs in GAERS.


Subject(s)
Electroencephalography , Epilepsy, Absence/genetics , Neurons/physiology , Receptors, GABA-B/physiology , Synaptic Transmission/physiology , Animals , Motor Cortex/physiology , Rats , Thalamic Nuclei/physiology
9.
J Physiol ; 517 ( Pt 3): 805-15, 1999 Jun 15.
Article in English | MEDLINE | ID: mdl-10358120

ABSTRACT

1. The existence of a non-negligible steady-state ('window') component of the low threshold, T-type Ca2+current (IT) and an appropriately large ratio of IT to ILeak conductance (i.e. gT/gLeak) have been shown to underlie a novel form of intrinsic bistability that is present in about 15 % of thalamocortical (TC) neurones. 2. In the present experiments, the dynamic clamp technique was used to introduce into mammalian TC neurones in vitro either an artificial, i.e. computer-generated, IT in order to enhance endogenous IT, or an artificial inward ILeak to decrease endogenous ILeak. Using this method, we were able to investigate directly whether the majority of TC neurones appear non-bistable because their intrinsic ionic membrane properties are essentially different (i.e. presence of a negligible IT 'window' component), or simply because they possess a gT or gLeak conductance that is insufficiently large or small, respectively. 3. The validity of the dynamic clamp arrangement and the accuracy of artificial IT were confirmed by (i) recreating the low threshold calcium potential (LTCP) with artificial IT following its block by Ni2+ (0.5-1 mM), and (ii) blocking endogenous LTCPs with an artificial outward IT. 4. Augmentation of endogenous IT by an artificial analog or introduction of an artificial inward ILeak transformed all non-bistable TC neurones to bistable cells that expressed the full array of bistability-mediated behaviours, i.e. input signal amplification, slow oscillatory activity and membrane potential bistability. 5. These results demonstrate the existence of a non-negligible IT 'window' component in all TC neurones and suggest that rather than being a novel group of neurones, bistable cells are merely representative of an interesting region of dynamical modes in the (gT, gLeak) parameter space that may be expressed under certain physiological or pathological conditions by all TC neurones and other types of excitable cells that possess an IT 'window' component with similar biophysical properties.


Subject(s)
Calcium Channels/physiology , Neurons/physiology , Thalamus/physiology , Animals , Calcium Channels, T-Type , Cats , Female , In Vitro Techniques , Male , Mammals , Membrane Potentials , Oscillometry , Patch-Clamp Techniques , Rats , Rats, Wistar
10.
Neuroscience ; 87(3): 541-50, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9758221

ABSTRACT

The dynamic clamp technique was used in thalamocortical neurons of the rat and cat dorsal lateral geniculate nucleus in vitro to investigate the effects of the hyperpolarization-activated cation current, Ih, and of its neuromodulation on burst firing and delta oscillations. Specific block of endogenous Ih using 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyridinium chloride (ZD7288) (300 microM) abolished the depolarizing "sag" response to negative current steps, markedly increased the latency and shortened the duration of the low-threshold Ca2+ potentials, and decreased the number of action potentials in the burst evoked by the low-threshold Ca2+ potential. Subsequent introduction of artificial Ih using the dynamic clamp re-instated the "sag" and all the original properties of the low-threshold Ca2+ potential. In the absence of ZD7288, introduction of artificial outward Ih with the intention of abolishing endogenous Ih removed the depolarizing "sag" and produced similar effects on the low-threshold Ca2+ potentials as those observed during the pharmacological block of Ih. Application of ZD7288 to thalamocortical neurons displaying delta oscillations led to a reduction in the voltage range of their existence or to a complete cessation of this behaviour. A subsequent introduction of artificial Ih re-enabled the generation of delta oscillations. In the presence of ZD7288, physiologically relevant positive shifts in the voltage-dependence of artificial Ih increased the amplitude and duration of the low-threshold Ca2+ potential and increased the likelihood of delta oscillations while negative shifts had opposite effects. These results highlight the important difference between the dependence of burst firing and oscillations on membrane potential and their dependence on the properties of Ih, and demonstrate that the modulation by Ih of low-threshold Ca2+ potentials and burst firing in thalamocortical neurons, as well as the ability of these neurons to generate delta oscillations, is more elaborate than previously described.


Subject(s)
Cerebral Cortex/cytology , Cerebral Cortex/physiology , Periodicity , Thalamus/cytology , Thalamus/physiology , 2-Amino-5-phosphonovalerate/pharmacology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Bicuculline/analogs & derivatives , Bicuculline/pharmacology , Cardiovascular Agents/pharmacology , Cats , Excitatory Amino Acid Antagonists/pharmacology , Female , GABA Antagonists/pharmacology , Geniculate Bodies/cytology , Geniculate Bodies/physiology , In Vitro Techniques , Male , Neurons/cytology , Neurons/drug effects , Organophosphorus Compounds/pharmacology , Patch-Clamp Techniques , Pyrimidines/pharmacology , Rats , Rats, Wistar , Sleep/physiology , Wakefulness/physiology
11.
Neuroscience ; 87(2): 519-23, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9740410

ABSTRACT

Thalamocortical neurons display a wide spectrum of activity patterns that are the expressions of the non-linear interactions between the various voltage-gated ion channels. Here, we show how bistable behaviour can emerge in these neurons, and how it is brought about by the steady-state residual ("window") component of IT, the low-threshold Ca2+ current. In particular, we present results that describe the dependence of bistability on two system parameters: the injected current and the leakage conductance. In addition, we provide a biophysical interpretation of these results by means of the properties of the electrical circuit representing the neuron membrane.


Subject(s)
Biophysics , Neurons/physiology , Thalamus/physiology , Algorithms , Biophysical Phenomena , Electric Stimulation , Electrophysiology , Kinetics , Membrane Potentials/physiology , Models, Neurological , Nonlinear Dynamics , Thalamus/cytology
12.
Physiol Meas ; 18(4): 401-10, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9413871

ABSTRACT

Sixteen formalin-fixed foetal livers were scanned in vitro using a new system for estimating volume from a sequence of multiplanar 2D ultrasound images. Three different scan techniques were used (radial, parallel and slanted) and four volume estimation algorithms (ellipsoid, planimetry, tetrahedral and ray tracing). Actual liver volumes were measured by water displacement. Twelve of the sixteen livers also received x-ray computed tomography (CT) and magnetic resonance (MR) scans and the volumes were calculated using voxel counting and planimetry. The percentage accuracy (mean +/- SD) was 5.3 +/- 4.7%, -3.1 +/- 9.6% and -0.03 +/- 9.7% for ultrasound (radial scans, ray volumes), MR and CT (voxel counting) respectively. The new system may be useful for accurately estimating foetal liver volume in utero.


Subject(s)
Liver/anatomy & histology , Algorithms , Animals , Female , Humans , Image Processing, Computer-Assisted , Liver/diagnostic imaging , Magnetic Resonance Imaging , Mice , Pregnancy , Tomography, X-Ray Computed , Ultrasonography
13.
Physiol Meas ; 18(1): 73-84, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9046539

ABSTRACT

A new system is described for estimating volume from a series of multiplanar 2D ultrasound images. Ultrasound images are captured using a personal computer video digitizing card and an electromagnetic localization system is used to record the pose of the ultrasound images. The accuracy of the system was assessed by scanning four groups of ten cadaveric kidneys on four different ultrasound machines. Scan image planes were oriented either radially, in parallel or slanted at 30 degrees to the vertical. The cross-sectional images of the kidneys were traced using a mouse and the outline points transformed to 3D space using the Fastrak position and orientation data. Points on adjacent region of interest outlines were connected to form a triangle mesh and the volume of the kidneys estimated using the ellipsoid, planimetry, tetrahedral and ray tracing methods. There was little difference between the results for the different scan techniques or volume estimation alogorithms, although, perhaps as expected, the ellipsoid results were the least precise. For radial scanning and ray tracing, the mean and standard deviation of the percentage errors for the four different machines were as follows: Hitachi EUB-240, -3.0 +/- 2.7%; Tosbee RM3, -0.1 +/- 2.3%; Hitachi EUB-415, 0.2 +/- 2.3%; Acuson, 2.7 +/- 2.3%.


Subject(s)
Kidney/anatomy & histology , Kidney/diagnostic imaging , Ultrasonography/instrumentation , Animals , Equipment Design , Mice , Phantoms, Imaging , Reproducibility of Results , Swine , Ultrasonography/methods , Video Recording
14.
J Physiol ; 505 ( Pt 3): 689-705, 1997 Dec 15.
Article in English | MEDLINE | ID: mdl-9457646

ABSTRACT

1. The mechanism underlying a novel form of input signal amplification and bistability was investigated by intracellular recording in rat and cat thalamocortical (TC) neurones maintained in slices and by computer simulation with a biophysical model of these neurones. 2. In a narrow membrane potential range centred around -60 mV, TC neurones challenged with small (10-50 pA), short (50-200 ms) current steps produced a stereotyped, large amplitude hyperpolarization (> 20 mV) terminated by the burst firing of action potentials, leading to amplification of the duration and amplitude of the input signal, that is hereafter referred to as input signal amplification. 3. In the same voltage range centred around -60 mV, single evoked EPSPs and IPSPs also produced input signal amplification, indicating that this behaviour can be triggered by physiologically relevant stimuli. In addition, a novel, intrinsic, low frequency oscillation, characterized by a peculiar voltage dependence of its frequency and by the presence of plateau potentials on the falling phase of low threshold Ca2+ potentials, was recorded. 4. Blockade of pure Na+ and K+ currents by tetrodotoxin (1 microM) and Ba2+ (0.1-2.0 mM), respectively, did not affect input signal amplification, neither did the presence of excitatory or inhibitory amino acid receptor antagonists in the perfusion medium. 5. A decrease in [Ca2+]o (from 2 to 1 mM) and an increase in [Mg2+]o (from 2 to 10 mM), or the addition of Ni2+ (2-3 mM), abolished input signal amplification, while an increase in [Ca2+]o (from 2 to 8 mM) generated this behaviour in neurones where it was absent in control conditions. These results indicate the involvement of the low threshold Ca2+ current (IT) in input signal amplification, since the other Ca2+ currents of TC neurones are activated at potentials more positive than -40 mV. 6. Blockade of the slow inward mixed cationic current (Ih) by 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium++ + chloride (ZD 7288)(100-300 microM) did not affect the expression of the large amplitude hyperpolarization, but abolished the subsequent repolarization to the original membrane potential. In this condition, therefore, input signal amplification was replaced by bistable membrane behaviour, where two stable membrane potentials separated by 15-30 mV could be switched between by small current steps. 7. Computer simulation with a model of a TC neurone, which contained only IT, Ih, K+ leak current (ILeak) and those currents responsible for action potentials, accurately reproduced the qualitative and quantitative properties of input signal amplification, bistability and low frequency oscillation, and indicated that these phenomena will occur at some value of the injected DC if, and only if, the 'window' component of IT (IT,Window) and the leak conductance (gLeak) satisfy the relation (dIT,Window/dV)max > gLeak. 8. The physiological implications of these findings for the electroresponsiveness of TC neurones are discussed, and, as IT is widely expressed in the central nervous system, we suggest that 'window' IT will markedly affect the integrative properties of many neurones.


Subject(s)
Calcium/physiology , Neurons/physiology , Thalamus/physiology , Action Potentials/physiology , Animals , Cats , Computer Simulation , Excitatory Postsynaptic Potentials/physiology , Female , In Vitro Techniques , Male , Models, Biological , Neurons/drug effects , Patch-Clamp Techniques , Potassium Channel Blockers , Pyrimidines/pharmacology , Rats , Rats, Wistar , Sodium Channel Blockers , Thalamus/cytology , Thalamus/drug effects
15.
J Physiol ; 505 ( Pt 3): 727-47, 1997 Dec 15.
Article in English | MEDLINE | ID: mdl-9457648

ABSTRACT

1. Intracellular sharp electrode current clamp and discontinuous single electrode voltage clamp recordings were made from thalamocortical neurones (n = 57) of the cat ventrobasal thalamus in order to investigate the mechanism underlying anomalous rectification. 2. Under current clamp conditions, voltage-current (V-I) relationships in a potential range of -55 to -110 mV demonstrated anomalous rectification with two components: fast rectification, which controlled the peak of negative voltage deviations, and time-dependent rectification. Time-dependent rectification was apparent as a depolarizing sag generated during the course of negative voltage deviations, was first formed at potentials in the range -60 to -70 mV, and was sensitive to 3 mM Cs+ (n = 6). Similarly, under voltage clamp conditions, instantaneous and steady-state I-V relationships demonstrated anomalous rectification. A slowly activating inward current with an activation threshold in the range of -65 to -70 mV formed time-dependent rectification. This current was sensitive to Cs+ (3 mM) (n = 3) and had properties similar to the slow inward mixed cationic current (Ih). 3. 4-(N-Ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium++ + chloride (ZD 7288) (100-300 microM) irreversibly blocked time-dependent rectification mediated by Ih (n = 23 of 25 neurones), and led to a hyperpolarization of the resting membrane potential (6.8 +/- 0.5 mV). In the presence of ZD 7288, V-I and I-V relationships, exhibited fast anomalous rectification, first activated from potential more negative than -80 mV. 4. Ba2+ (100 microM) (n = 8), in the continuous presence of ZD 7288, reversibly linearized peak V-I and instantaneous I-V relationships over a potential range of -70 to -120 mV, and led to a membrane depolarization (13.3 +/- 4.2 mV) or tonic inward current (192 +/- 36 pA). 5. The co-application of ZD 7288 and Ba2+ revealed a depolarizing sag in negative voltage deviations under current clamp conditions, or a large inward current with kinetics two to three times slower than those of Ih under voltage clamp conditions. This novel form of time-dependent rectification was first apparent at potentials more negative than about -85 mV, was sensitive to 5 mM Cs+ (n = 4), and is termed Ih,slow. Ih,slow tail currents reversed between -65.3 and -56.6 mV (with potassium acetate electrodes, n = 3) or -57.6 and -50.3 mV (with KCl electrodes, n = 3). 6. Computer simulations confirmed that the pattern of anomalous rectification in thalamocortical neurones of the cat ventrobasal thalamus is mediated by the concerted action of Ih and a Ba(2+)-sensitive current with properties similar to an inwardly rectifying K+ current (IKIR).


Subject(s)
Neurons/physiology , Potassium Channels, Inwardly Rectifying , Thalamus/physiology , Animals , Barium/physiology , Cats , Computer Simulation , Female , In Vitro Techniques , Male , Membrane Potentials/physiology , Patch-Clamp Techniques , Potassium Channel Blockers , Potassium Channels/physiology , Pyrimidines/pharmacology , Thalamus/cytology
16.
Br J Obstet Gynaecol ; 103(10): 1015-20, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8863701

ABSTRACT

OBJECTIVE: To measure fetal lung volume using a computer based, enhanced, 3-dimensional ultrasound imaging system. DESIGN: An observational study. SETTING: The Fetal Medicine Unit at Guys Hospital, London. PARTICIPANTS: Twenty healthy women with a singleton pregnancy between 24 and 36 weeks of gestation were scanned on one occasion during pregnancy using an ultrasound based 3-dimensional imaging system. All delivered at term with weights above the 10th centile for gestation. RESULTS: Total lung volume increased exponentially with gestational age. Right lung volume measured consistently greater than left lung volume. CONCLUSIONS: The use of this new enhanced 3-dimensional imaging system allows for estimations of fetal lung volume. Preliminary data confirm that fetal lung volume, measured by a computerised 3-dimensional ultrasound imaging system increased exponentially with gestational age. The use of this system has obvious application in the further study of lung growth in utero and possible clinical application in disease states where fetal lung growth may be impaired.


Subject(s)
Lung/embryology , Ultrasonography, Prenatal/methods , Female , Fetal Organ Maturity , Fetus/anatomy & histology , Gestational Age , Humans , Image Processing, Computer-Assisted , Lung/diagnostic imaging , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third
17.
Phys Med Biol ; 41(9): 1809-21, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8884913

ABSTRACT

Volume measurements are useful in many branches of science and medicine. They are usually accomplished by acquiring a sequence of cross sectional images through the object using an appropriate scanning modality, for example x-ray computed tomography (CT), magnetic resonance (MR) or ultrasound (US). In the cases of CT and MR, a dividing cubes algorithm can be used to describe the surface as a triangle mesh. However, such algorithms are not suitable for US data, especially when the image sequence is multiplanar (as it usually is). This problem may be overcome by manually tracing regions of interest (ROIs) on the registered multiplanar images and connecting the points into a triangular mesh. In this paper we describe and evaluate a new discreet form of Gauss' theorem which enables the calculation of the volume of any enclosed surface described by a triangular mesh. The volume is calculated by summing the vector product of the centroid, area and normal of each surface triangle. The algorithm was tested on computer-generated objects, US-scanned balloons, livers and kidneys and CT-scanned clay rocks. The results, expressed as the mean percentage difference +/- one standard deviation were 1.2 +/- 2.3, 5.5 +/- 4.7, 3.0 +/- 3.2 and -1.2 +/- 3.2% for balloons, livers, kidneys and rocks respectively. The results compare favourably with other volume estimation methods such as planimetry and tetrahedral decomposition.


Subject(s)
Algorithms , Magnetic Resonance Imaging , Mathematics , Phantoms, Imaging , Tomography, X-Ray Computed , Ultrasonography , Humans , Kidney/anatomy & histology , Kidney/diagnostic imaging , Liver/anatomy & histology , Liver/diagnostic imaging
18.
Int J Hyperthermia ; 12(2): 271-8, 1996.
Article in English | MEDLINE | ID: mdl-8926394

ABSTRACT

A system is described for delivering transurethral hyperthermia to the prostate. The system used a helical coil antennae powered by a 434 MHz generator. The antennae was housed in a disposable 22 Ch Foley catheter with water passed down the centre of the winding of the antennae and returned between the antennae and inner wall of the catheter. The flow rate of the circulating water could be varied. The position of the antennae was adjustable with respect to the balloon, essentially altering the length of the antennae. Urethral wall temperature was measured with a thermocouple passed down a small tube moulded into the outer wall of the catheter. Rectal temperature was measured using thermocouples placed in grooves machined into a custom made perspex rectal applicator. A computer program displayed the temperature and controlled the power to the generator. The SAR around the catheter was measured in a polyacrylamide gel phantom. However this does not take into account the effects blood flow and thermal conduction which may have important clinical implications. In order to investigate the actual temperature within the prostate during treatment, a group of patients underwent intraprostatic thermometry.


Subject(s)
Hyperthermia, Induced/methods , Prostatic Hyperplasia/therapy , Acrylic Resins/metabolism , Catheterization/methods , Humans , Hyperthermia, Induced/instrumentation , Male , Microwaves , Temperature , Urethra/metabolism , Urinary Bladder/metabolism
19.
Ultrasound Med Biol ; 22(5): 561-72, 1996.
Article in English | MEDLINE | ID: mdl-8865553

ABSTRACT

A system is described for calculating volume from a sequence of multiplanar 2D ultrasound images. Ultrasound images are captured using a video digitising card (Hauppauge Win/TV card) installed in a personal computer, and regions of interest transformed into 3D space using position and orientation data obtained from an electromagnetic device (Polhemus, Fastrak). The accuracy of the system was assessed by scanning 10 water filled balloons (13-141 mL), 10 kidneys (147-200 mL) and 16 fetal livers (8-37 mL) in water using an Acuson 128XP/10 (5 MHz curvilinear probe). Volume was calculated using the ellipsoid, planimetry, tetrahedral and ray tracing methods and compared with the actual volume measured by weighing (balloons) and water displacement (kidneys and livers). The mean percentage error for the ray tracing method was 0.9 +/- 2.4%, 2.7 +/- 2.3%, 6.6 +/- 5.4% for balloons, kidneys and livers, respectively. So far the system has been used clinically to scan fetal livers and lungs, neonate brain ventricles and adult prostate glands.


Subject(s)
Image Processing, Computer-Assisted/methods , Kidney/diagnostic imaging , Liver/diagnostic imaging , Ultrasonography/methods , Algorithms , Animals , Fetus , Humans , In Vitro Techniques , Models, Anatomic , Swine
20.
Br J Urol ; 76(1): 73-6, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7544207

ABSTRACT

OBJECTIVE: To compare the effects of microwave hyperthermia in benign prostatic hypertrophy (BPH) to sham treatment. PATIENTS AND METHODS: The trial included 96 patients with proven symptomatic bladder outflow obstruction (BOO) caused by BPH. Patients underwent a full subjective and objective assessment (including urodynamics) before inclusion and again 3 and 6 months later. They were randomly assigned to receive 1 h of microwave hyperthermia or a sham treatment. Of the 96 patients, 93 were assessed at 3 months and 62 at 6 months after treatment. RESULTS: There was no statistically significant difference in the objective measures of BOO between the treated and control groups of patients. There was an improvement of approximately 40% in all the subjective measures, but there was no significant difference between the treated and control groups. CONCLUSION: Microwave hyperthermia, within the parameters defined in this trial, resulted in no significant difference from sham treatment in subjective or objective outcome.


Subject(s)
Hyperthermia, Induced/methods , Microwaves/therapeutic use , Prostatic Hyperplasia/therapy , Aged , Humans , Male , Multivariate Analysis , Treatment Outcome , Urinary Retention/therapy , Urination
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