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Biomedical subjects

Yoram Cohen

Publications and source records attributed to Yoram Cohen.

At least 19 recordsLinked to original sources

Preoperative radio-chemotherapy treatment in locally advanced rectal carcinoma. Results of 8-year follow-up.

BACKGROUND: Preoperative radio-chemotherapy (RCT) may play an important role in decreasing local recurrence and possibly improving survival for patients with advanced rectal carcinoma. PATIENTS AND METHODS: Between 1995 and 1998 we treated 30 patients (pts) (median age 61.5 years) with advanced low rectal cancer. Radiotherapy was administered using a 10-MV linear accelerator delivering a total dose of 45 Gy to the pelvis over 5 weeks. 5-FU (500 mg/m2/d i.v.) was given concomitantly on days 1-3 and 29-31. Surgery was performed 2-4 weeks after RCT and included abdomino-perineal resection (APR) in 15 pts, anterior resection in 11 pts, transanal resection in 1 pt, and explorative laparotomy in 1 pt; 2 pts refused surgery. RESULTS: There were no serious toxicities associated with RCT. Mild to moderate transient radiation dermatitis was noted in 3 pts, and grade II diarrhea in 4 pts. Postoperative pathologic staging was as follows: no tumor found (CR): 4 pts, MAC B1 (T2N0M0): 5 pts, MAC B2 (T3N0M0): 17 pts, B3 (vaginal involvement): 1 pt, MAC C2 (T3N1M0): 2 pts, and MAC D: 1 pt. Necrosis and/or fibrosis was noted as a prominent histopathologic feature. CONCLUSION: Preoperative RCT in this series of 30 pts with advanced rectal cancer was well tolerated and associated with a high response rate (13% CR, 17% PR, 57% NC). 5-year overall survival was 70%, and 8-year survival was 58%.

Adenocarcinoma↗

Diffusion measurements for molecular capsules: pulse sequences effect on water signal decay.

Diffusion NMR and, more recently, diffusion ordered spectroscopy (DOSY) are gaining popularity as efficient tools for the characterization of supramolecular systems in solution. Here, using diffusion NMR of hydrogen-bond molecular capsules, we demonstrate that the use of different diffusion sequences may have a dramatic effect on exchanging peaks. In fact, we found that the signal decay of the water peak in [(1a)(6)(H(2)O)(8)] is monoexponential in the pulsed gradient spin-echo (PGSE) and stimulated echo (PGSTE) sequences and biexponential in the longitudinal eddy current delay (LED) and the bipolar longitudinal eddy current delay (BPLED) sequences, routinely used in modern DOSY experiments. By performing these diffusion measurements on molecular capsules, in which water is not part of the molecular capsules, we demonstrate that this phenomenon is observed only for water molecules that exchange between two sites that differ considerably in their diffusion coefficients. Degeneration of the LED or the BPLED sequences into PGSTE-type sequences by shortening the te period resulted in the disappearance of the extra slow diffusing component. The origin, as well as the implications of the different results obtained from conventional diffusion sequences, such as the PGSE and PGSTE as compared with the LED and BPLED sequences generally used in DOSY experiments, are briefly discussed.

Diffusion↗

Pharmacokinetics of a slow-release formulation of soybean isoflavones in healthy postmenopausal women.

Pharmacokinetic studies of soybean isoflavones have shown that following oral ingestion, the two major isoflavones, daidzin and genistin, are hydrolyzed in the intestine, rapidly absorbed into the peripheral circulation, and eliminated from the body with a terminal half-life of 7-8 h. These characteristics make maintenance of steady-state plasma isoflavone concentrations difficult to attain unless there is repeated daily ingestion of foods or supplements containing isoflavones. In an attempt to sustain more constant plasma isoflavone concentrations, a new slow-release formulation of a soybean isoflavone extract was prepared by microencapsulation with a mixture of hydroxypropylcellulose and ethylcellulose to alter its dissolution characteristics. In vitro experiments confirmed slow aqueous dissolution of isoflavones from this formulation when compared with the conventional isoflavone extract. The pharmacokinetics of this slow-release isoflavone extract was studied in 10 healthy postmenopausal women after oral administration of a single capsule containing the equivalent of 22.3 mg of genistein and 7.47 mg of daidzein expressed as aglycons. A comparison of the key pharmacokinetic parameters obtained in this study with those established in extensive studies performed previously in this laboratory indicated that the mean residence time of genistein and daidzein increased 2-fold with microencapsulation. These findings are indicative of a decreased rate of absorption, consistent with the observed slow in vitro dissolution rate. These findings show that it is feasible to employ polymer matrices that slow the aqueous dissolution for preparing sustained-release formulations of soy isoflavones. Further studies to optimize such formulations are warranted.

Chromatography, High Pressure Liquid↗

Diffusion NMR spectroscopy in supramolecular and combinatorial chemistry: an old parameter--new insights.

Intermolecular interactions in solution play an important role in molecular recognition, which lies at the heart of supramolecular and combinatorial chemistry. Diffusion NMR spectroscopy gives information over such interactions and has become the method of choice for simultaneously measuring diffusion coefficients of multicomponent systems. The diffusion coefficient reflects the effective size and shape of a molecular species. Applications of this technique include the estimation of association constants and mapping the intermolecular interactions in multicomponent systems as well as investigating aggregation, ion pairing, encapsulation, and the size and structure of labile systems. Diffusion NMR spectroscopy can also be used to virtually separate mixtures and screen for specific ligands of different receptors, and may assist in finding lead compounds.

Combinatorial Chemistry Techniques↗

Probing the molecular interaction of chymotrypsin with organophosphorus compounds by 31P diffusion NMR in aqueous solutions.

In the present study, we applied for the first time (31)P diffusion NMR to resolve different species obtained by the addition of organophosphorus compounds (OP) such as diisopropyl phosphorofluoridate (DFP) or 1-pyrenebutyl phosphorodichloridate (PBPDC) to alpha-chymotrypsin (Cht). (31)P diffusion NMR was used since the products of these reactions constitute a mixture of OP-covalent conjugates of the enzyme and OP-containing hydrolysis products that have noninformative (1)H NMR spectra. It was shown that the peak, attributed to the covalent native diisopropylphosphoryl-Cht (DIP-Cht) conjugate by chemical shift considerations, has a greater diffusion coefficient (D = (0.65 +/- 0.01) x 10(-5) cm(2) s(-1)) than expected from its molecular mass (approximately 25 kDa). This peak was therefore suggested to consist of at least two superimposed signals of diisopropyl phosphoryl (DIP) pools of high and low molecular weights that happen to have the same chemical shift. This conclusion was substantiated by the use of DMSO-d(6) that separated the overlapping signals. Diffusion measurements performed on the extensively dialyzed and unfolded DIP-Cht conjugate still resulted in a high diffusion coefficient ((0.30 +/- 0.05) x 10(-5) cm(2) s(-1)) relative to the assumed molecular mass. This observation was attributed to a dynamic dealkylation at the OP moiety (i.e., aging) that occurred during the relatively long diffusion measurements, where DIP-Cht was converted to the corresponding monoisopropyl phosphoryl Cht (MIP-Cht) conjugate. Homogeneous aged forms of OP-Cht were obtained by use of DFP and heat-induced dealkylation of DIP-Cht, and by PBPDC that provided the aged form via the hydrolysis of a P-Cl bond (PBP-Cht). The thermally stable aged conjugates enabled a reliable determination of the diffusion coefficients over several days of data acquisition, and the values found were (0.052 +/- 0.002) x 10(-5) cm(2) s(-1) and (0.054 +/-0.004) x 10(-5) cm(2) s(-1) for the MIP-Cht and the PBP-Cht adducts, respectively, values in the range expected for a species with a molecular weight of 25 kDa. The advantages and limitations of (31)P diffusion NMR in corroborating the type of species that prevail in such systems are briefly discussed.

Animals↗

Normal white matter development from infancy to adulthood: comparing diffusion tensor and high b value diffusion weighted MR images.

PURPOSE: To evaluate the sensitivity of high b value diffusion weight magnetic resonance imaging (DWI) in detecting normal white matter maturation, compare it to conventional diffusion tensor imaging (DTI), and to obtain normative quantitative data using this method. MATERIALS AND METHODS: High b value DWI (b(max) = 6000 sec/mm(2)) using q-space analysis and conventional DTI (b = 1000 sec/mm(2)) were performed on 36 healthy subjects aged 4 months to 23 years. Fractional-anisotropy (FA), apparent-displacement, and apparent-probability values were measured in all slices and in six regions of interest (ROIs) of large fiber tracks. Values were correlated with each other and with age using regression analysis. RESULTS: FA, displacement, and probability indices from all slices were highly correlated with each other (r > 0.87, P < 0.0001) and with age (r > 0.82, P < 0.0001). All age-related changes in the six pre-determined ROIs were best fitted by mono-exponential functions. Changes in the splenium extended to a later age when compared with the genu of the corpus-callosum, while the centrum semi-ovale demonstrated the latest changes with age. CONCLUSIONS: High b-value DWI and DTI showed changes in white matter from infancy through adulthood. However, high b-value detects a signal that is likely to originate mainly from the intra-axonal water population, and thus may represent different aspects of development and different sensitivity to pathology.

Adolescent↗

Measurement of talent in team handball: the questionable use of motor and physical tests.

Testing for selection is one of the most important fundamentals in any multistep sport program. In most ball games, coaches assess motor, physical, and technical skills on a regular basis in early stages of talent identification and development. However, selection processes are complex, are often unstructured, and lack clear-cut theory-based knowledge. For example, little is known about the relevance of the testing process to the final selection of the young prospects. The purpose of this study was to identify motor, physical, and skill variables that could provide coaches with relevant information in the selection process of young team handball players. In total, 405 players (12-13 years of age at the beginning of the testing period) were recommended by their coaches to undergo a battery of tests prior to selection to the Junior National Team. This number is the sum of all players participating in the different phases of the program. However, not all of them took part in each testing phase. The battery included physical measurements (height and weight), a 4 x 10-m running test, explosive power tests (medicine ball throw and standing long jump), speed tests (a 20-m sprint from a standing position and a 20-m sprint with a flying start), and a slalom dribbling test. Comparisons between those players eventually selected to the Junior National Team 2-3 years later with those not selected demonstrated that only the skill test served as a good indicator. In all other measurements, a wide overlap could be seen between the results of the selected and nonselected players. It is suggested that future studies investigate the usefulness of tests reflecting more specific physical ability and cognitive characteristics.

Adolescent↗

Colorimetric approach to high-throughput mutation analysis.

High-throughput genomic mutation screening for primary tumors has characteristically been expensive, labor-intensive, and inadequate to detect low levels of mutation in a background of wild-type signal. We present a new, combined PCR and colorimetric approach that is inexpensive, simple, and can detect the presence of 1% mutation in a background of wild-type. We compared manual dideoxy sequencing of p53 for eight lung cancer samples to a novel assay combining a primer extension step and an enzymatic colorimetric step in a 96-well plate with covalently attached oligonucleotide sequences. For every sample, we were able to detect the presence or absence of the specific mutation with a statistically significant difference between the sample optical density (OD) and the background OD, with a sensitivity and specificity of 100%. This assay is straightforward, accurate, inexpensive, and allows for rapid, high-throughput analysis of samples, making it ideal for genomic mutation or polymorphism screening studies in both clinical and research settings.

Biological Assay↗

Self-recognition, structure, stability, and guest affinity of pyrogallol[4]arene and resorcin[4]arene capsules in solution.

In the present study, we used diffusion NMR to probe the structures and characteristics of the products obtained from the self-assembly of resorcin[4]arenes 1a and 1b and pyrogallol[4]arenes 2a and 2b in CDCl(3) solutions. It was found that all four molecules self-assemble into hexameric capsules. The hexameric capsules of pyrogallol[4]arenes 2a and 2b were found to be more stable than the capsules of resorcin[4]arenes 1a and 1b in polar media. We also studied the role of water molecules in the self-assembly of the different capsules and found that water molecules are part of the hexameric capsules of resorcin[4]arenes 1a and 1b but not in the capsules of pyrogallol[4]arenes 2a and 2b. It was found that the self-assembly process between the resorcin[4]arenes and pyrogallol[4]arenes proceeds with self-recognition. When mixing two macrocycles of different types in a chloroform solution, no heterohexamers are formed, only the capsule constructed from the same macrocycle is detected. However, when two resorcin[4]arenes (i.e., 1a and 1b) or two pyrogallol[4]arenes (i.e., 2a and 2b) are mixed, heterohexamers are formed over time. In addition, we found that resorcin[4]arenes and pyrogallol[4]arenes differ significantly in their guest affinity. The capsules of 1a and 1b can accommodate both the tertiary alkylamines and their respective ammonium salts, while the capsules of 2a and 2b encapsulate only the neutral tertiary alkylamines.

Journal Article↗

Exon 15 BRAF mutations are uncommon in melanomas arising in nonsun-exposed sites.

PURPOSE: An activating point mutation of the BRAF oncogene has been identified in a high proportion of cutaneous nevi and cutaneous melanomas, but its frequency in melanomas arising from the mucosa of head and neck is unknown. EXPERIMENTAL DESIGN: We tested 17 malignant mucosal melanomas of the head and neck for the thymine (T)-->adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using direct sequencing and a newly developed assay that uses a novel primer extension method (Mutector assay). We also tested 21 cutaneous melanomas, including 13 arising from sun-exposed sites and 8 from a nonsun-exposed site, the vulvar skin. RESULTS: The 1796T-->A mutation was detected in only 1 (6%) of the sinonasal melanomas. As for cutaneous melanomas, a BRAF mutation was detected in 8 (62%) of the tumors arising in sun-exposed sites but in none (0%) of vulvar melanomas. CONCLUSIONS: In contrast to cutaneous melanomas arising in sun-exposed sites, mucosal melanomas of the head and neck do not frequently harbor an activating mutation of BRAF. This finding additionally supports the view that the various subtypes of melanoma are not equivalent and that distinct genetic alterations may underlie well recognized differences in risk factors and behavioral patterns. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new strategies are developed that target specific genetic alterations.

Adenine↗

Associations between androgen receptor CAG repeat length and sperm morphology.

BACKGROUND: The number of (trinucleotide) CAG repeats within the androgen receptor (AR) gene is inversely correlated with transcriptional activity of testosterone-target genes. Although abnormally long CAG repeats are strongly associated with male infertility, it is unclear whether CAG repeat length polymorphism can affect androgen receptor activity and sperm parameters. To explore the previously suggested association between CAG repeats and male fertility, we conducted this prospective cohort study. METHODS: We enrolled 172 men attending the IVF unit in Shaare-Zedek Medical Center. Sperm concentration, motility and morphology and the number of CAG repeats in the AR gene were measured. RESULTS: Mean CAG repeat length was greater in teratozoospermia (<14% normal forms, strict criteria) than in the normal morphology group [mean +/- 95% confidence interval (CI) 22.19 +/- 0.38 versus 21.25 +/- 0.28, P = 0.02]. Logistic regression models showed that longer CAG repeats were associated with abnormal sperm morphology [odds ratio for percentage of normal forms per unit increase in CAG repeat length 1.14 (95% CI 1.01-1.28), P = 0.04]. No association was found between CAG repeat length and sperm concentration or motility. CONCLUSIONS: We found a positive correlation between CAG repeat length and teratozoospermia. This finding validates the concept that AR function is inversely regulated by length of its CAG repeat tract.

Adult↗

Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules.

BACKGROUND: Fine needle aspiration (FNA) is routinely used in the preoperative evaluation of thyroid nodules, but subsequent patient management is often complicated by the inability to decisively recognize malignancy on cytologic grounds alone. Activating mutations of the BRAF oncogene commonly occur in papillary thyroid carcinomas (PTCs) but not in other types of benign and malignant thyroid lesions. Mutational analysis of FNAs could enhance selection of thyroid nodules for surgical removal. METHODS: Ninety-five excised PTCs along with 49 corresponding FNAs were evaluated for BRAF mutations by a newly developed assay that uses a novel primer extension method (MutectorR assay) and by direct sequencing. An additional 42 FNAs from thyroid nodules that were excised based on a suspicion of malignancy were also evaluated. RESULTS: BRAF mutations were identified in 36 of the 95 (38%) excised PTCs. By histological subtype, BRAF mutations were more common in conventional PTCs than in the follicular variant (67% versus 12%; P < 0.0001; chi(2)). Analysis of the preoperative FNAs accurately reflected BRAF status of the resected PTC in 46 of the 49 paired samples (94% concordance). In FNA samples grouped according to the preoperative cytologic findings (malignant, n = 25; benign, n = 11; and indeterminate, n = 55), a BRAF mutation confirmed the diagnosis of PTC in 72% of carcinomas within the malignant group, and it established the diagnosis of PTC in 16% of carcinomas within the indeterminate group. BRAF mutations were not detected in FNAs from 32 benign thyroid lesions. Direct sequencing and the MutectorR assay yielded completely concordant results. CONCLUSIONS: BRAF mutations are common in conventional PTCs, and they are specific for PTC. A BRAF mutation can be reliably detected in cells aspirated from a thyroid nodule suggesting a role for this marker in the preoperative evaluation of thyroid nodules.

Biopsy, Fine-Needle↗

CDC91L1 (PIG-U) is a newly discovered oncogene in human bladder cancer.

Genomic amplification at 20q11-13 is a common event in human cancers. We isolated a germline translocation breakpoint at 20q11 from a bladder cancer patient. We identified CDC91L1, the gene encoding CDC91L1 (also called phosphatidylinositol glycan class U (PIG-U), a transamidase complex unit in the glycosylphosphatidylinositol (GPI) anchoring pathway), as the only gene whose expression was affected by the translocation. CDC91L1 was amplified and overexpressed in about one-third of bladder cancer cell lines and primary tumors, as well as in oncogenic uroepithelial cells transformed with human papillomavirus (HPV) E7. Forced overexpression of CDC91L1 malignantly transformed NIH3T3 cells in vitro and in vivo. Overexpression of CDC91L1 also resulted in upregulation of the urokinase receptor (uPAR), a GPI-anchored protein, and in turn increased STAT-3 phosphorylation in bladder cancer cells. Our findings suggest that CDC91L1 is an oncogene in bladder cancer, and implicate the GPI anchoring system as a potential oncogenic pathway and therapeutic target in human cancers.

Animals↗

Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis.

Follicular epithelial cell-derived thyroid tumors are common neoplasms comprised mainly of benign thyroid adenomas, follicular thyroid cancers, and papillary thyroid cancers (PTCs). Hypermethylation of the tumor suppressor gene RASSF1A and activating mutation of BRAF gene have been reported recently in thyroid cancers. To additionally investigate the roles of these two epigenetic/genetic alterations in thyroid tumor progression, we examined their occurrences and relationship in both benign and malignant thyroid neoplasms. With real-time quantitative methylation-specific PCR, we found that 4 of 9 (44%) benign adenomas, 9 of 12 (75%) follicular thyroid cancers tumors, and 6 of 30 (20%) of PTC tumors harbored promoter methylation in > or = 25% of RASSF1A alleles. Additional quantitative analysis revealed RASSF1A methylation only in BRAF mutation-negative PTCs. A similar inverse correlation of RASSF1A methylation with BRAF mutation was seen in thyroid tumor cell lines. Our results, therefore, suggest that epigenetic inactivation of RASSF1A through aberrant methylation is an early step in thyroid tumorigenesis. Like the previously reported mutually exclusive relationship between BRAF mutation and other Ras pathway components such as RET/PTC rearrangement, a mutually exclusive relationship also exists between BRAF mutation and RASSF1A methylation in thyroid tumorigenesis.

Cell Line, Tumor↗

The interaction of water molecules with purple membrane suspension using 2H double-quantum filter, 1H and 2H diffusion nuclear magnetic resonance.

Bacteriorhodopsin is a membrane protein of the purple membrane (PM) of Halobacterium salinarum, which is isolated as sheets of highly organized two-dimensional hexagonal microcrystals and for which water molecules play a crucial role that affects its function as a proton pump. In this paper we used single- and double-quantum (2)H NMR as well as (1)H and (2)H diffusion NMR to characterize the interaction of water molecules with the PM in D(2)O suspensions. We found that, under the influence of a strong magnetic field on a concentrated PM sample (0.61 mM), the PM sheets affect the entire water population and a residual quadrupolar splitting (upsilon(q) approximately 5.5 Hz, 298 K, at 11.7 T) is observed for the D(2)O molecules. We found that the residual quadrupolar coupling, the creation time in which a maximal DQF signal was obtained (tau(max)), and the relative intensity of the (2)H DQF spectrum of the water molecules in the PM samples (referred to herein as NMR order parameters) are very sensitive to temperature, dilution, and chemical modifications of the PM. In concentrated PM samples in D(2)O, these NMR parameters seem to reflect the relative organization of the PM. Interestingly, we have observed that some of these parameters are sensitive to the efficiency of the trimer packing, as concluded from the apo-membrane behavior. The data for dionized blue membrane, partially delipidated sample, and detergent-treated PM show that these D(2)O NMR order parameters, which are magnetic field dependent, are sensitive to the structural integrity of the PM. In addition, we revealed that heating the PM sample inside or outside the NMR magnet has, after cooling, a different effect on the NMR characteristics of the water molecules in the concentrated PM suspensions. The difference in the D(2)O NMR order parameters for the PM samples, which were heated and cooled in the presence and in the absence of a strong magnetic field, corroborates the conclusions that the above D(2)O order parameters are indirect reflections of both microscopic and macroscopic order of the PM samples. In addition, (1)H NMR diffusion measurements showed that at least three distinct water populations could be identified, based on their diffusion coefficients. These water populations seem to correlate with different water populations previously reported for the PM system.

Apoproteins↗

Microsphere-induced embolic stroke: an MRI study.

Despite the many studies of the middle cerebral artery occlusion (MCAO) model, efficient therapy for stroke is still lacking, emphasizing the need for further development and characterization of experimental stroke models. In the present study, the rather unexplored multifocal microsphere-induced stroke model in rats was characterized by multiparametric MRI. We induced microembolic infarction in a group of Sprague-Dawley rats by injecting a dose of about 1000 50-microm polyethylene microspheres intracranially from the external carotid artery. Diffusion-, perfusion-, and T(2)-weighted MRI were used to evaluate the infarct development during and following the first 3 hr after microsphere injection (N = 20). The animals were also imaged at 12-hr (N = 8), 24-hr (N = 17), and 48-hr (N = 5) time points. After the final imaging time point, the brains were removed and sectioned into 2-mm-thick slices, and infarct volumes were measured by 2,3,4-triphenyltetrazolium chloride (TTC) staining. From calculated apparent diffusion coefficient (ADC) maps, a volume of reduced ADC appeared 0.5-1.0 hr postinjection, and by the 3-hr time point the volume of ADC reduction had increased to a size of 5% +/- 1% (mean +/- SEM) of the brain hemisphere. The lesion volume increased significantly (P < 0.01) to 16% +/- 2% of the hemisphere volume at the 12-hr time point, while at 24 hr the lesion (15% +/- 2% of the hemisphere) was also significantly larger (P < 0.001) than at 3 hr. The perfusion deficit resulting from the microsphere injection was immediate, going from a cerebral blood flow index (CBF(i)) of 74% +/- 3% at the time of microsphere injection to 68% +/- 2% of the contralateral mean at 3 hr (P < 0.05), to 55% +/- 4% of the contralateral values at 12 hr (P < 0.05), and to 57% +/- 2% of the contralateral mean at 24 hr (P < 0.001). The lesion development in the microsphere-induced stroke model was found to be slower than in the MCAO model, and continued up to the 24-48-hr time point.

Animals↗

The effect of rotational angle and experimental parameters on the diffraction patterns and micro-structural information obtained from q-space diffusion NMR: implication for diffusion in white matter fibers.

Diffusion NMR may provide, under certain experimental conditions, micro-structural information about confined compartments totally non-invasively. The influence of the rotational angle, the pulse gradient length and the diffusion time on the diffusion diffraction patterns and q-space displacement distribution profiles was evaluated for ensembles of long cylinders having a diameter of 9 and 20 microm. It was found that the diffraction patterns are sensitive to the rotational angle (alpha) and are observed only when diffusion is measured nearly perpendicular to the long axis of the cylinders i.e., when alpha= 90 degrees +/- 5 degrees under our experimental conditions. More importantly, we also found that the structural information extracted from the displacement distribution profiles and from the diffraction patterns are very similar and in good agreement with the experimental values for cylinders of 20 microm or even 9 microm, when data is acquired with parameters that satisfy the short gradient pulse (SGP) approximation (i.e., delta -->0) and the long diffusion time limit. Since these experimental conditions are hardly met in in vitro diffusion MRI of excised organs, and cannot be met in clinical MRI scanners, we evaluated the effect of the pulse gradient duration and the diffusion time on the structural information extracted from q-space diffusion MR experiments. Indeed it was found that, as expected, accurate structural information, and diffraction patterns are observed when Delta is large enough so that the spins reach the cylinders' boundaries. In addition, it was found that large delta results in extraction of a compartment size, which is smaller than the real one. The relevance of these results to q-space MRI of neuronal tissues and fiber tracking is discussed.

Diffusion Magnetic Resonance Imaging↗