Supramolecular solubilisation of hydrophilic dyes by using individual dendritic branches.

Individual dendritic branches can solubilise hydrophilic dyes in apolar media. The functional group at the focal point of the dendritic branch plays a key role in the dye uptake process. Supramolecular interactions between carboxylic acid and amine groups have been shown to be effective in enabling efficient solubilisation to occur. The necessary complementarity of this interaction is further illustrated by a series of control experiments. The extent of dendritic branching (i.e. dendritic generation) plays a key role in controlling the extent of dye uptake, with higher-generation dendritic branches exhibiting more efficient uptake at lower concentrations. UV/Visible spectroscopic methods have shown that the dendritic branches, in addition to the tuning of the extent of dye uptake, also tune the optical properties of the solubilised dye and this provides further insight into the interactions occurring between the solubilised dye and the individual dendritic branches. Furthermore, it is shown that suitably functionalised dendritic branches can transport hydrophilic dyes through an apolar phase and deliver them continuously into an aqueous medium.

Efficacy, safety and tolerability of anagrelide in the treatment of essential thrombocythaemia.

BACKGROUND: Essential thrombocythaemia (ET) has an associated risk of thrombotic and haemorrhagic complications, which can be minimised by control of the platelet count. Anagrelide selectively lowers the platelet count, however, there is little Australasian experience with its use and scant data on symptom control. AIMS: To evaluate the efficacy of anagrelide for platelet reduction and symptom control in a broad cohort of patients with well-defined ET, and to determine the safety and tolerability in such a population. METHODS: Seventeen patients with ET and a platelet count > 600 x 10(9)/L were prospectively enrolled. The evaluable four males and 12 females with a median age of 58 years (range 14-79) included ten patients (63%) previously treated with two or more agents and 12 patients (75%) who had failed other therapies. The median follow-up was seven months (range 15 days to 36 months). RESULTS: Anagrelide, in an average dose of 1.9 mg/day, reduced the platelet count from a mean of 728 x 10(9)/L (95% CI 611-845 x 10(9)/L) to 412 x 10(9)/L (95% CI 319-504 x 10(9)/L) (p < 0.001) and maintained it at this level. Fourteen patients (88%) had a platelet reduction to < 600 x 10(9)/L. All symptomatic patients had improvement in symptoms attributable to thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in a total of three patients (19%), including one death from an intracerebral haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a median of 151 days. Side effects included palpitations, abdominal pain and cough. CONCLUSIONS: Anagrelide is efficacious and safe in ET, both for platelet and symptom control. Minor side effects are common, however, tend to occur early and resolve spontaneously in most cases.

Safe mobilization of normal progenitors in advanced chronic myeloid leukemia with intensive chemotherapy and granulocyte-colony stimulating factor.

Twenty-one patients with advanced chronic myeloid leukemia (late chronic phase (n = 8), accelerated phase (n = 11) and blast crisis (n = 2)) were treated with idarubicin, cytarabine, and etoposide followed by G-CSF and subsequent collection of peripheral blood progenitor cells in the early recovery phase. Treatment was reasonably well tolerated with no deaths or intensive care admissions. Despite the advanced phase of disease and heavy pretreatment with cytotoxics and interferon-alfa, 11 of 21 patients (52%) achieved a cytogenetic response. Of the nine major cytogenetic responses (complete (n = 3) and partial (n = 6)), seven achieved adequate progenitor collections for consideration for autologous transplantation. The only predictor of response was disease duration (P = 0.02). With a median follow-up of 1171 days from treatment it appears unlikely that G-CSF contributed to disease progression. Survival post-IcE was predicted by disease stage (P = 0.0001). Intensive chemotherapy followed by G-CSF allowed adequate yields of predominantly Philadelphia chromosome negative progenitor cells to be obtained from one-third of patients with advanced CML.

Myelodysplasia.

Myelodysplasia or myelodysplastic syndromes represent a heterogeneous group of bone marrow disorders characterized by dysmaturation, cytopenias, and a propensity for leukemic transformation. Although universally adopted, the French-American-British classification still has several limitations and an inability to categorize all patients. Refinements in morphologic and histologic interpretation in addition to the use of scoring systems may improve diagnostic and prognostic capability. Cytogenetics and molecular genetic abnormalities are providing clues to the fundamental pathogenesis of myelodysplastic syndromes. However, the lesions responsible for initiation or disease progression are as yet unresolved. Although chemotherapy and allogeneic transplantation may be used in selected patients, the mainstay of therapy remains supportive care, with differentiating therapy being largely disappointing so far and the role of hematopoietic growth factors remaining unresolved.

Ideal versus human observer for long-tailed point spread functions: does deconvolution help?

The ideal observer represents a Bayesian approach to performing detection tasks. Since such tasks are frequently used as a prototype tasks for radiological imaging systems, the detectability measured at the output of an ideal detector can be used as a figure of merit to characterize the imaging system. For the detectability achieved by the ideal observer to be a good figure of merit, it should predict the ability of the human observer to perform the same detection task. Of great general interest, especially to the medical community, are imaging devices with long-tailed point spread functions (PSFs). Such PSFs may occur due to septal penetration in collimators, veiling glare in image intensifiers or scattered radiation in the body. We have investigated the effect that this type of PSF has on human visual signal detection and whether any improvement in performance can be gained by deconvolving the tails of the PSF. For the ideal observer, it is straightforward to show that the performance is independent of any linear, invertible deconvolution filter. Our psychophysical studies show, however, that performance of the human observer is indeed improved by deconvolution. The ideal observer is, therefore, not a good predictor of human observer performance for detection of a signal imaged through a long-tailed PSF. We offer some explanations for this discrepancy by using some characteristics of the visual process and suggest a standard of comparison for the human observer that takes into account these characteristics. A look at the performance of the non-prewhitening (npw) ideal observer, before and after deconvolution, also brings some good insight into this study.

Detection of breast abnormalities on teleradiology transmitted mammograms.

The authors conducted an observer performance study to compare breast lesion detection of conventional mammography (CM) with teleradiology (TE) transmitted mammograms. One hundred four abnormal, single-projection mammographic images were transmitted by teleradiology. Abnormalities included 11 cases with skin thickening or retraction, 48 cases with microcalcifications, and 52 with parenchymal masses. The CM and TE images were reviewed by four mammographers who indicated the type and location of abnormalities and a level of confidence for their diagnostic decisions. For each of three detection tasks--skin and nipple abnormalities, microcalcifications, and masses--receiver operating characteristic curve analysis was performed for individual readers and all readers as a group. For detecting skin and nipple abnormalities, readers performed significantly better with CM than with TE (z = 2.05, P = less than 0.04). However, no significant differences were found among readers for detection of either microcalcifications or masses. Further improvements in hardware and imaging parameters may improve detection of soft tissue abnormalities. Further evaluation is necessary to determine whether teleradiology might be applicable to breast cancer screening.

Computer-simulated lung nodules in digital chest radiographs for detection studies.

Computer simulations of lung nodules overcome many shortcomings of creating radiographs using anthropomorphic nodule phantoms for lung nodule detection studies, but these algorithms can be cumbersome and involved. A simple, fast, and flexible computer program to simulate lung nodules in digital chest radiographs for detection studies is reported. To verify the realism of the simulated nodules, a psychophysical study and a statistical study were conducted. In the psychophysical study, six radiologists and four nonradiologists were asked to distinguish between 17 real lung nodules and 17 computer-simulated lung nodules shown in eight radiographs. The results show that the computer-simulated lung nodules are indistinguishable visually from real lung nodules. Using parameters from the Rose model of vision, results show that the simulated and real nodules are the same statistically. Thus, besides visual validity, statistical analysis in confirming the validity of the simulated lung nodules is included.

Evaluation of a new method for verifying truth of diagnosis in clinical research.

Having a good methodology for establishing truth of diagnosis would be invaluable to researchers in radiology. A protocol to verify the truth of diagnosis of clinical images to be used in radiologic research has been proposed that specifies six classes, depending on how the diagnosis is verified. In this paper it was evaluated. The protocol was applied to sixty-nine liver-spleen scans. Using five of the possible six classes of the protocol, 42% of the scans were verifiable. Twenty-eight per cent of the cases could be verified by non-physicians using the first four classes of the protocol. In 96% of a sample of these cases, their diagnosis matched that of the physicians. Radiologists are needed for the last two classes. However, using three radiologists to investigate Class V protocol procedures only eight (16%) more cases were clearly classifiable. Class VI was not investigated. The protocol met its objectives of reducing physician involvement and developing a detailed methodology. The difficulties inherent in verification of diagnosis are also discussed, and suggestions for improving the protocol are proposed.

Design and testing of artifact-suppressed adaptive histogram equalization: a contrast-enhancement technique for display of digital chest radiographs.

One of the goals of our research in the field of digital radiography has been to develop contrast-enhancement algorithms for eventual use in the display of chest images on video devices with the aim of preserving the diagnostic information presently available with film, some of which would normally be lost because of the smaller dynamic range of video monitors. The ASAHE algorithm discussed in this article has been tested by investigating observer performance in a difficult detection task involving phantoms and simulated lung nodules, using film as the output medium. The results of the experiment showed that the algorithm is successful in providing contrast-enhanced, natural-looking chest images while maintaining diagnostic information. The algorithm did not effect an increase in nodule detectability, but this was not unexpected because film is a medium capable of displaying a wide range of gray levels. It is sufficient at this stage to show that there is no degradation in observer performance. Future tests will evaluate the performance of the ASAHE algorithm in preparing chest images for video display.

Spinal cord compression due to metastatic disease: diagnosis with MR imaging versus myelography.

To determine the efficacy of magnetic resonance (MR) imaging and myelography for the diagnosis of spinal cord compression due to metastatic disease, the authors prospectively examined 70 patients who had known or suspected spinal involvement by malignancy. Most MR examinations consisted of T1-weighted sagittal imaging of the entire spine, with additional sequences as needed for clarification. Extradural masses were found in 46 patients, 25 of whom had cord compression. For extradural masses causing cord compression, the sensitivity and specificity of MR imaging was .92 and .90, respectively, compared with .95 and .88 for myelography. For extradural masses without cord compression the sensitivity and specificity of MR imaging was .73 and .90, versus .49 and .88 for myelography. MR imaging was much more sensitive for metastases to bone (.90 vs .49), as expected. MR imaging is an acceptable alternative to myelography for diagnosing spinal cord compression and is preferable as a first study because it is noninvasive and better tolerated.

Computer-assisted analysis of mammographic clustered calcifications.

A total of 127 biopsy-proven clustered mammographic calcifications were diagnosed and evaluated using multiple parameters. The results were subjected to computer analysis. The number of calcifications/cm2 was the most important parameter. Less than 10 calcifications/cm2 resulted in an 82% chance of being benign while 10 or more calcifications/cm2 had a 44% chance of being malignant. The average distance between the calcifications in the cluster was also significant, with a 92% chance of being benign if greater than 1 mm and a 52% chance of being malignant if less than 1 mm. The remaining parameters did not yield statistically significant results, but there were trends which suggest that less than 10 clustered calcifications that are regular in size and shape and orderly in appearance tend to be benign while disorderly clusters tend to be malignant. In order to decrease the number of false positive biopsies and improve the cost-effectiveness of screening mammography, radiologists should consider 6-month follow-up mammography as a reasonable alternative for clustered calcifications that appear benign.

Intraoperative arteriography: comparison of conventional screen-film with photostimulable imaging plate radiographs.

This prospective study compared images obtained with a photostimulable imaging plate with matched images obtained with a conventional screen-film combination in 26 patients undergoing intraoperative arteriography. Diagnostic accuracy of the two techniques was assessed objectively, and image quality was assessed subjectively. In 16 patients (62%), the radiation exposure was reduced by 50% for the imaging plate technique by decreasing the mAs level generally used for the screen-film combination. Because of the dynamic range of the imaging plate system, no repeat examinations were necessary, while 12% of the screen-film studies had to be repeated because of over- or under-penetration. Imaging plate studies required 6% more time for processing than screen-film studies. Receiver-operating-characteristic analysis indicated no difference in diagnostic accuracy between the two imaging techniques. Subjective evaluation also revealed no difference in observer preference for imaging plate or screen-film studies. The imaging plate technique is an excellent alternative to screen-film studies in the operating room.

Comparison of conventional fluorescein angiography film images with a cathode ray tube display.

We evaluated the effectiveness of cathode ray tube (CRT) displays in the transfer of diagnostic information to the ophthalmologist. Retinal fluorescein angiography images were used and data were taken using the receiver operating characteristic experimental paradigm. Three ophthalmologists with experience ranging from two to 12 years participated in the study. Sixty-eight images were selected from proof sheets of 800 original images. Next, these images were digitized, then each set was shown on its respective display (slide projection for the proof sheet images and CRT for the digital images). These 68 images were from a variety of patients and represented a broad range of normal and abnormal retinas (including diabetic retinopathy, hypertension independent of diabetes, and sickle-cell disease). Results show (1) that there is no difference between the systems in terms of diagnostic accuracy; (2) that certainty of diagnosis was not a function of the system; and (3) that although there was an effect due to experience of the ophthalmologist, it did not affect diagnosis accuracy. We conclude that CRT displays at conventional video resolutions can deliver the needed diagnostic information as well as film. We also hypothesize that digital enhancement techniques can increase the available diagnostic information beyond that of film.

FEASIBLE (I): The PC software package for feature evaluation and system inspection by logged experiments.

FEASIBLE is an MS-DOS software package which can be used for the evaluation of: Picture Archiving and Communication System (PACS) components; diagnostic image quality; and image manipulation and representation techniques. The FEASIBLE software allows the user to design any psychophysical study in detail in the fields mentioned above, to execute an arbitrary number of sessions and to statistically analyse the results by way of the Receiver Operating Characteristic (ROC) technique. FEASIBLE consists basically of three modules: DESIGN, which allows the user to set up an experiment; EXECUTION, which allows the user to execute the experimental sessions based on the design entered in the DESIGN module and stored in the program's database; and, STATISTICS, which allows various statistical analyses on the data collected during the psychophysical sessions (including the calculation of ROC curves and related parameters) and can provide a graphical presentation of the results. FEASIBLE has been designed to support experts and those who have little knowledge of psychophysical experiments. This paper discusses the background, structure and possibilities of the FEASIBLE package at this point (version 1.2, May 1988).

Computed radiographic evaluation of simulated pulmonary nodules. Preliminary results.

We evaluated the capabilities of a computed radiography system (CRS) and a standard radiography system (SRS) in the detection of simulated solitary pulmonary lung nodules of various sizes and contrast. A phantom simulated the pulmonary anatomy, and specially shaped plexiglass disks were externally mounted to simulate solitary pulmonary nodules of different diameters and thicknesses. ROC curves were generated based on the performance of each of the radiologists observing each film set. In this preliminary study, the overall performance for both the CRS and the SRS were comparable in detecting simulated pulmonary nodules.

Detection of small radiation sources: the effect of mode of count-rate presentation.

We used an observer-performance study to compare four different modes of presenting count-rate data from a radiation detector. Observers searched for small, concealed radioactive sources using a hand-held radiation-detector probe. The modes of count-rate presentation were a ratemeter, howler, multichannel scaler, and HRM III. The HRM III calculates the statistical significance of the difference between current and previous count rates and presents the result as an audio signal. We tested six observers with each mode of count-rate presentation, calculated receiver operating characteristic (ROC) curves, and used the areas under the ROC curves to compare the different modes. Observer performance was better with the multichannel scaler and HRM III than with either the ratemeter or the howler. The results suggest that observer performance with devices that use ratemeters or howlers can be enhanced by improving the mode of count-rate presentation.

Conventional vs computed radiography: evaluation of myelography.

A prospective study was performed to compare the diagnostic efficacy of conventional film-screen (FS) imaging with computed radiography (CR) in myelography. Forty examinations were done with both methods. Digital myelography was found to have diagnostic accuracy equal to that of conventional film-screen examinations.