Gray matter textural heterogeneity as a potential in-vivo biomarker of fine structural abnormalities in Asperger syndrome.

Brain imaging studies contribute to the neurobiological understanding of Autism Spectrum Conditions (ASC). Herein, we tested the prediction that distributed neurodevelopmental abnormalities in brain development impact on the homogeneity of brain tissue measured using texture analysis (TA; a morphological method for surface pattern characterization). TA was applied to structural magnetic resonance brain scans of 54 adult participants (24 with Asperger syndrome (AS) and 30 controls). Measures of mean gray-level intensity, entropy and uniformity were extracted from gray matter images at fine, medium and coarse textures. Comparisons between AS and controls identified higher entropy and lower uniformity across textures in the AS group. Data reduction of texture parameters revealed three orthogonal principal components. These were used as regressors-of-interest in a voxel-based morphometry analysis that explored the relationship between surface texture variations and regional gray matter volume. Across the AS but not control group, measures of entropy and uniformity were related to the volume of the caudate nuclei, whereas mean gray-level was related to the size of the cerebellar vermis. Similar to neuropathological studies, our study provides evidence for distributed abnormalities in the structural integrity of gray matter in adults with ASC, in particular within corticostriatal and corticocerebellar networks. Additionally, this in-vivo technique may be more sensitive to fine microstructural organization than other more traditional magnetic resonance approaches and serves as a future testable biomarker in AS and other neurodevelopmental disorders.

The influence of finite aperture and frequency response of ultrasonic hydrophone probes on the determination of acoustic output.

The influence of finite aperture and frequency response of piezoelectric ultrasonic hydrophone probes on the Thermal and Mechanical Indices was investigated using a comprehensive acoustic wave propagation model. The experimental verification of the model was obtained using a commercially available, 8 MHz, dynamically focused linear array and a single element, 5 MHz, focused rectangular source. The pressure-time waveforms were recorded using piezoelectric polymer hydrophone probes of different active element diameters and bandwidths. The nominal diameters of the probes ranged from 50 to 500 microm and their usable bandwidths varied between 55 and 100 MHz. The Pulse Intensity Integral (PII), used to calculate the Thermal Index (TI), was found to increase with increasing bandwidth and decreasing effective aperture of the probes. The Mechanical Index (MI), another safety indicator, was also affected, but to a lesser extent. The corrections needed were predicted using the model and successfully reduced the discrepancy as large as 30% in the determination of PII. The results of this work indicate that by accounting for hydrophones' finite aperture and correcting the value of PII, all intensities derived from the PII can be corrected for spatial averaging error. The results also point out that a caution should be exercised when comparing acoustic output data. In particular, hydrophone's frequency characteristics of the effective diameter and sensitivity are needed to correctly determine the MI, TI, and the total acoustic output power produced by an imaging transducer.

Hydrophones' effective diameter measurements as a quasi-continuous function of frequency.

The spatial averaging effect is strongly dependent on the active aperture of the hydrophone probes used to measure ultrasound fields. An experimental method was developed to determine the effective diameter of the probes as a quasi-continuous function of frequency. The implementation of the method utilizes the time delay spectrometry (TDS) technique and a set of focused acoustic sources. The use of focused sources ensured plane wave conditions for the whole frequency range and TDS eliminated all the reflections from the water tank boundaries. This approach allows effective diameter of circular aperture hydrophones to be determined as a quasi-continuous function of frequency up to 40 MHz. The measurements were performed for both needles and membrane designs having nominal diameters ranging from 50 to 500 microm. The results were successfully employed in the development of spatial averaging correction algorithms. Current efforts are being focused on extension of the frequency range up to 60 MHz by using a novel measurement technique termed time gating frequency analysis.

Calibration of ultrasonic hydrophone probes up to 100 MHz using time gating frequency analysis and finite amplitude waves.

A number of ultrasound imaging systems employs harmonic imaging to optimize the trade off between resolution and penetration depth and center frequencies as high as 15 MHz are now used in clinical practice. However, currently available measurement tools are not fully adequate to characterize the acoustic output of such nonlinear systems primarily due to the limited knowledge of the frequency responses beyond 20 MHz of the available piezoelectric hydrophone probes. In addition, ultrasound hydrophone probes need to be calibrated to eight times the center frequency of the imaging transducer. Time delay spectrometry (TDS) is capable of providing transduction factor of the probes beyond 20 MHz, however its use is in practice limited to 40 MHz. This paper describes a novel approach termed time gating frequency analysis (TGFA) that provides the transduction factor of the hydrophone probes in the frequency domain and significantly extends the quasi-continuous calibration of the probes up to 60 MHz. The verification of the TGFA data was performed using TDS calibration technique (up to 40 MHz) and a nonlinear calibration method (up to 100 MHz). The nonlinear technique was based on a novel wave propagation model capable of predicting the true pressure-time waveforms at virtually any point in the field. The spatial averaging effects introduced by the finite aperture hydrophones were also accounted for. TGFA calibration results were obtained for different PVDF probes, including needle and membrane designs with nominal diameters from 50 to 500 micro m. The results were compared with discrete calibration data obtained from an independent national laboratory and the overall uncertainty was determined to be +/-1.5 dB in the frequency range 40-60 MHz and less than +/-1 dB below 40 MHz.

Nonlinear propagation model for ultrasound hydrophones calibration in the frequency range up to 100 MHz.

To facilitate the implementation and verification of the new ultrasound hydrophone calibration techniques described in the companion paper (somewhere in this issue) a nonlinear propagation model was developed. A brief outline of the theoretical considerations is presented and the model's advantages and disadvantages are discussed. The results of simulations yielding spatial and temporal acoustic pressure amplitude are also presented and compared with those obtained using KZK and Field II models. Excellent agreement between all models is evidenced. The applicability of the model in discrete wideband calibration of hydrophones is documented in the companion paper somewhere in this volume.

1-60 MHz measurements in focused acoustic fields using spatial averaging corrections.

The purpose of this research was to develop, implement and verify a measurement technique enabling rapid and dependable characterization of ultrasound hydrophone probes beyond 20 MHz. The technique employs focused acoustic sources to optimize signal-to-noise ratio and spatial averaging correction model to account for the finite aperture of the hydrophone probes. To minimize calibration time, substitution technique was chosen and its applicability was tested up to 60 MHz. The overall uncertainty of the measurements was on the order of +/- 1 dB. The results are presented for both needle and membrane type PVDF hydrophones having effective diameters ranging from 130-1200 microns. The fundamental limitations of the technique were determined and it is shown that the spatial averaging error is governed by the cross-section of the beam in the focal plane and the ratio of the effective diameters of the reference and tested hydrophone probes. The technique developed is being extended to frequencies beyond 60 MHz.

Hydrophone spatial averaging corrections from 1 to 40 MHz.

The purpose of this study was to develop and experimentally verify a practical spatial averaging model for frequencies up to 40 MHz. The model is applicable to focused sources of circular geometry, accounts for the effects of hydrophone probe finite aperture, and allows calibration by substitution to be performed when the active elements of reference and tested hydrophone probes differ significantly. Several broadband sources with focal numbers between 3 and 20 were used to produce ultrasound fields with frequencies up to 40 MHz. The effective diameters of the ultrasonic hydrophone probes calibrated in the focal plane of the sources ranged from 150 to 500 microm. Prior to application of the spatial averaging corrections, the hydrophones with diameters smaller than that of the reference hydrophone exhibited experimentally determined absolute sensitivities higher than the true ones. This discrepancy increased with decreasing focal numbers and increasing frequency. It was determined that the error was governed by the cross-section of the beam in the focal plane and the ratio of the effective diameters of the reference and tested hydrophone probes. In addition, the error was found to be reliant on the frequency-dependent effective hydrophone radius. After applying the spatial averaging correction, the overall uncertainty in the hydrophone calibration was on the order of +/-1 dB. The model developed is being extended to be applicable to frequencies beyond 40 MHz, which are becoming increasingly important in diagnostic ultrasound imaging applications.

Improved classification of psychiatric mood disorders using a feedforward neural network.

Our aim was to use a neural network model for classifying psychiatric mood disorders. In approaching this interdisciplinary task, the concern was not to build a more biologically plausible model, but to test the computational capabilities of an existent one. The multilayer perceptron was chosen as a model, trained and tested using both theoretical and real cases. The classification proved to be good, but we are aware of the fact that both training and testing should be performed in the future only on real data, as the way to get a true picture of the system's performance.

Translocations (4p+; 6q-) and (12q-; Xp+) in blastic phase of a Ph1-positive chronic myeloid leukemia.

This paper reports a 28-year-old woman with Philadelphia chromosome (Ph1)-positive chronic myeloid leukemia (CML) who developed two marrow cell lines during the blastic phase: one with the translocation (12;X) (q 11;p22) and the other with the translocation (4;6) (p 16;q 25). The literature on involvement of chromosomes 12 and X in translocations and the appearance of 6 q- aberration in CML is summarized. The relationship between the 6 q-aberration and the blast cells with lymphoid appearance in the plastic phase of CML is discussed.

Cytoenzymochemical changes in acute leukemia cells under cytostatic treatment.

Cytomorphologic and cytoenzymochemical changes occurring in leukemic blastic cells of bone marrow and peripheral blood were studied concomitantly in 180 cases of acute leukemia treated with one or more cytostatics, in various association related to the main cytologic type. Cellular effects due to monochemotherapy in various types of acute leukemia varied depending on the cytostatic dose, duration of treatment, and sensitivity of blastic cells to the cytostat. The expression of cellular sensitivity was marked by megaloblastosis of myeloid elements, cell gigantism and intranuclear and cytoplasmic vacuolization. Resistance to cytostatics was demonstrated both by the morphologic aspect of blastic cells which remained unchanged and by their overloading with glycogen, lipids and peroxidases. The relationships between posttherapeutic cellular changes and clinical parameters are discussed.

Incidence and significance of micronuclei in pernicious anemia.

The incidence of micronuclei in bone marrow erythroblasts of patients with pernicious anemia ranged between 0.5-5.6% as compared with the value of 0-0.5% noted in hematologically healthy patients. The mechanism of formation and the possible significance of micronuclei in megaloblastic anemia are briefly discussed.

Criteria for immunosuppressive treatment (corticotherapy) in the early stage of chronic viral hepatitis.

Thirty-five patients showing quatitative deviations from normal of the M and G immunoglobulin (Ig) fractions were selected for study from a larger group of patients with viral hepatitis. In 15 of the 35 cases, most of which showed high IgM and/or IgG serum levels, moderate doses of prednisone were administered for 60 days. Determinations of Ig levels were performed before and after corticotherapy, two and four months respectively after the onset of the acute viral hepatitis. The rest of 20 patients were used as controls. In the cases in which the clinical and biological parameters indicated an improvement after treatment, the initial high IgM titers showed a tendency to decrease while in those with severe evolution, IgM levels increased. A similar behaviour of IgM titers, though less marked, was also noticed in the control group, of untreated patients. These variations are assumed to predict the further favourable of severe course of the disease; Ig variations and particularly the IgM ones, might be useful criteria for the selection of cases with high risk of developing chronic hepatitis, so that corticotherapy could be applied in the early stages, to prevent the progress to more severe forms of the disease.

Hematologic and histologic experimental investigations on the therapeutic effect of leukotrophin.

The paper aims at evidencing the stimulating effect on hematopoietic stem cells exerted by the thymus extract "Leukotrophin", prepared by Ellem Laboratory, Milan, Italy. Investigation of the hematologic and histologic parameters allowed the follow up of alterations occurring in bone marrow, blood and tissues of the irradiated animals, treated and untreated as compared with the unirradiated and untreated controls. Regeneration was more active in the groups of animals irradiated and treated with Leukotrophin than in the irradiated and untreated controls. A maximal regeneration of the myeloid series, prevalently of the erythrocytic line, was found 9 days after irradiation.

Sickle-cell disease. Two cases in a Romanian family.

Hemoglobin S is rarely found in Caucasians, especially in its homozygous expression. The authors report two cases of homozygotes for Hb S diagnosed in a Romanian family. Ten subjects were investigated, belonging to three generations of the same family, and the following results were obtained: two cases of homozygotes for Hb S; five cases of heterozygotes; three normal subjects. One of the two subjects homozygous for Hb S, a girl aged six, had a severe clinical evolution, typical for homozygous drepanocytosis. The second case, a sister of the first aged two, had a less severe evolution, without splenomegaly and thrombotic accidents. The heterozygote subjects showed no clinical symptoms. The two cases of homozygous Hb S reported are the first cases of sickle-cell disease described in Romania.