John S. Fleming

A technique for the absolute measurement of activity using a gamma camera and computer.

Describes a general method for the measurement of radioactivity in an organ using anterior, posterior and lateral views. Its application to liver colloid imaging is described as the liver/spleen ratio is widely used as an indication of cirrhosis.

Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid

Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (51Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r=0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner-Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study.

Long-term retention deficits in two cases of disproportionate retrograde amnesia

The status of very long-term retention, together with detailed brain imaging correlates, is presented in two patients with disproportionately dense retrograde amnesia. The first patient suffered a severe closed head injury and was left with dense autobiographical amnesia for events that she had experienced prior to her injury. She showed relatively mild, patchy memory impairment on standard anterograde memory tests. Postinjury autobiographical memory was relatively spared. However, postinjury long-term knowledge acquisition was significantly impaired. The second patient also suffered a severe head injury and was left with marked retrograde amnesia for events that she had experienced prior to her injury. She also showed relatively mild, patchy impairment on standard anterograde memory tests. Using specially designed tests, this patient showed normal immediate learning and delayed recall using a range of materials, but displayed significantly faster rate of forgetting over a period of 6 weeks than control subjects who were matched on initial delayed levels of retention. In both cases, there was major pathology in the region of the left temporal lobe, with lateral structures being more affected than medial structures. Our findings provide further evidence relating to the independence of certain anterograde and retrograde memory mechanisms, and support recent observations (De Renzi & Lucchelli, 1993) that link some instances of retrograde amnesia to impairment in very long-term retention. The possibility is raised that some forms of retrograde amnesia, such as the present cases, represent a type of disconnection syndrome, whereby visual-semantic and other associations are disconnected from verbal representations of such associations. Lesions to intrahemispheric fasciculi or similar association fibers, in combination with lesions to critical anterior or posterior cerebral structures, may play an important role in such a disconnection.

Fractional deposition from a jet nebulizer: How it differs from a metered dose inhaler

The fractional deposition from an Inspiron Mini-Neb jet nebulizer was assessed in six normal and two asthmatic subjects using technetium-99m-labelled millimicrospheres of human serum albumin suspended in saline. Sixty-six per cent of activity was retained in the apparatus tubing, 20% exhaled, 2% deposited in the mouth and 12% was retained in the lungs. The nebulizer fractional deposition therefore differs from the findings reported for a metered dose inhaler (Newman et al. 1981; Spiro et al. 1984), where 80-85% of particles leaving the cannister deposits in the mouth, and only 5-10% in the apparatus. The lung fraction from a nebulizer is, however, similar to the 9-11% from an MDI.

In silico modeling of asthma

The incidence of asthma is increasing throughout the world, especially among children, to the extent that it has become a medical issue of serious global concern. Appropriately, numerous pharmacologic drugs and clinical protocols for the treatment and prophylaxis of the disease have been reported. From a scientific perspective, a review of the literature suggests that the targeted delivery of an aerosol would, in a real sense, enhance the efficacy of an inhaled medicine. Therefore, in accordance with published data we have developed a mathematical description of disease-induced effects of disease on airway morphology. A morphological algorithm defining the heterogeneity of asthma has been integrated with a computer code that formulates the behavior and fate of inhaled drugs. In this work, predicted drug particle deposition patterns have been compared with SPECT images from experiments with healthy human subjects (controls) and asthmatic patients. The asthma drug delivery model simulations agree with observations from human testing. The results indicate that in silico modeling provides a technical foundation for addressing effects of disease on the administration of aerosolized drugs, and suggest that modeling should be used in a complementary manner with future inhalation therapy protocols.

Humidification as an adjunct to chest physiotherapy in aiding tracheo-bronchial clearance in patients with bronchiectasis

Humidification of inspired air or oxygen is frequently utilized by respiratory physiotherapists to relieve sputum retention. Cold water, jet nebulizing humidifiers are in widespread use but there has been no previous attempt to investigate the efficacy of this treatment. We have performed a single-blind, cross-over study to quantify the effect of humidification as an adjunct to chest physiotherapy. Seven patients with bronchiectasis completed the trial, with a mean (range) age of 51 years (41-64 years) and mean (range) percent of predicted FEV1 of 46% (29-76%). On 2 days, separated by 1 week, subjects were randomly allocated to humidification or no humidification as a precursor to an optimal chest physiotherapy regimen. A radio-aerosol of human serum albumin millimicrospheres labelled with 99mTechnetium was used to measure sputum clearance by serial gamma camera images. Serial measurements of sputum weight and FEV1 were also recorded. Humidification (30 min) was followed by postural drainage (20 min) with the subject using the forced expiration technique to assist clearance. When humidification was combined with physiotherapy there was a significant increase in total wet weight of sputum (P less than 0.05) with a median (range) increase of 6 g (-9-15.5 g); and a significant increase in total radiolabel clearance (P less than 0.05) with a median (range) increase of 8.7% (1-13%), compared to physiotherapy alone. This study demonstrates that the use of cold water, jet nebulizing humidifiers significantly increases tracheo-bronchial clearance above that of an optimal physiotherapy regimen alone in bronchiectasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Semi-automated tabulation of the 3D topology and morphology of branching networks using CT: application to the airway tree

Detailed information on biological branching networks (optical nerves, airways or blood vessels) is often required to improve the analysis of 3D medical imaging data. A semi-automated algorithm has been developed to obtain the full 3D topology and dimensions (direction cosine, length, diameter, branching and gravity angles) of branching networks using their CT images. It has been tested using CT images of a simple Perspex branching network and applied to the CT images of a human cast of the airway tree. The morphology and topology of the computer derived network were compared with the manually measured dimensions. Good agreement was found. The airways dimensions also compared well with previous values quoted in literature. This algorithm can provide complete data set analysis much more quickly than manual measurements. Its use is limited by the CT resolution which means that very small branches are not visible. New data are presented on the branching angles of the airway tree.

Evaluation of the accuracy and precision of lung aerosol deposition measurements from planar radionuclide imaging using simulation

Planar images of known, theoretical distributions of radioaerosol in the lung have been simulated using lung models derived from magnetic resonance studies on human subjects. Total lung activity was evaluated from the simulated images together with the absolute penetration index (PI) and a relative value expressed as a fraction of that in a simulated ventilation image. The accuracy and precision of these measurements were calculated by comparison with the true values used in the simulation. Total activity was assessed with systematic errors within 5% and precision within 6.5%. Measured PIs varied only slowly with true PI and inter-model variation masked changes between measurements on the different distributions. The relative PI reduced inter-model variation and provided significant differences between all the distributions. PI was significantly affected by misalignment of the lung region of interest. The conducting airways deposition fraction (CADF) used in the simulation correlated linearly with the fractional activity in a central lung region, allowing CADF to be estimated with a precision of 21%.

LUNG DEPOSITION OF PARTICLES BY AIRWAY GENERATION IN HEALTHY SUBJECTS: THREE-DIMENSIONAL RADIONUCLIDE IMAGING AND NUMERICAL MODEL PREDICTION

Multi- modality medical imaging enables measurement of the three-dimensional spatial distribution of inhaled, radiolabelled aerosol within the human lung. Using a conceptual model of spatial lung morphology, this data may be transformed to provide information on deposition by airway generation in the conducting airways. This methodology has been used to study intrapul- monary deposition patterns in control subjects for two polydisperse aerosols produced by jet-type nebulisers of mass median aerodynamic diameter (MMAD) 1. 8 and 6.8 pm. Comparison between derived experimental results and those from computer modelling shows reasonable agreement for total body, oropharynx and lung deposition and also for the difference in deposition pattern between the two aerosols. However, experiment suggests significantly less deposition in the central airways than is predicted by modelling. The new methodology has considerable potential in the fields of inhalation therapy and deposition modelling though more detailed validation is still required. 0 1998 Elsevier Science Ltd. All rights reserved

A technique for the deconvolution of the renogram

The renogram in its standard form does not express the renal handling of Hippuran in its simplest and most explicit form. The curve obtained, R(t), is a convolution of the input function from the blood to the kidney, I(t), and the impulse response function of the kidney, H(t). H(t) is the response to a bolus injection and represents the renal handling in its simplest form. It can be calculated by deconvolution since I(t) and R(t) can both be obtained in the investigation. A method involving Laplace transforms is used.