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[Signal changes of the bone marrow in MRI under long-term treatment with granulocyte colony-stimulating factors].

PURPOSE: Recurrent infections in patients with glycogen storage disease (GSD) type Ib resulting from an associated neutropenia are frequently treated with granulocyte colony-stimulating factors (G-CSF). The aim of this study was to evaluate the changes occurring in bone marrow by magnetic resonance imaging (MRI) in these patients. MATERIAL AND METHODS: The distal femoral and tibial bones of six patients with GSD Ib were evaluated by MRI. Four of these patients were treated with G-CSF for at least 3.9 to a maximum of 8.2 years (mean 5.8 years). The imaging sequences encompassed spin-echo as well as short-time inversion recovery sequences. 4 of the 6 patients had bone marrow aspirations. RESULTS: The patients who had undergone therapy with G-CSF showed a marked increase in signal strength in STIR sequences which encompassed the entire medullar cavity. In T1-weighted images these areas were hypointense. Biopsies obtained from these patients showed a bone marrow hypercellularity. The patients without G-CSF therapy showed the same signal intensity changes but with a more discrete and localized pattern in the metaphyseal cavities. CONCLUSION: In subjects with GSD Ib, an increased myelopoetic activity of the bone marrow which is intensified under long-term treatment with G-CSF can be demonstrated by MRI.

Adolescent↗

A perfectly symmetric lac operator binds the lac repressor very tightly.

A completely symmetric DNA segment has been constructed that binds the lactose repressor of Escherichia coli 10-fold more tightly than does the natural lactose operator sequence. This tight-binding operator is an inverted repeat of a 15-base-pair segment from the left half of the natural operator sequence, the inversion being about the point indicated by the arrow shown below: (sequence in text) where the upper sequence is the natural operator and the lower sequence is the symmetric operator. The increased affinity of repressor for this symmetric sequence supports the idea that the tetrameric repressor is designed for a two-module binding to DNA, presumably via two (or two pairs) of its identical subunits. The natural operator is apparently "flawed" by "incorrect" base pairs in the right operator half and by an "incorrect" spacing between the operator halves with respect to maximal repressor binding.

Base Sequence↗

A sequential response method of studing complex behavior in animals and its application to the measurement of drug effects.

A behavioral testing method was demonstrated to be applicable to the study of detrimental drug effects on complex behavior in rats. The method required the subject (S) to respond in a certain sequence to four identical response sites spaced 90 degrees apart within a cylindrical test compartment. After each S was shaped to perform its one particular sequence within this quadrilaterally symmetrical environment, and its performance was brought to a stable level, drug effects were then studied on a battery of such Ss whose sequential response habits were representative of a continuum of sequence complexity. Experiments with a drug which induces hallucinatory and confusional states in man showed that the method yields in the rat quantitative measures of detrimental behavioral effects in terms of dose-response and dose-time relationships in addition to providing an estimate of the interactive effect between drug dose and behavioral complexity. It was found that for a given magnitude of behavioral detriment, drug dose and behavioral complexity of sequence were inversely related. That is, a S required to perform a simple sequence needed a larger drug dose to interfere with its habit a unit amount that did a S with a more complex one; or, expressed another way, a given drug dose had a greater behavioral effect the more complex the sequence. Finally, an empirical ranking of response sequences along a functional behavioral complexity dimension was presented.

Animals↗

Magnetic resonance imaging of multiple sclerosis: a study of pulse-technique efficacy.

Forty-two patients with the clinical diagnosis of multiple sclerosis were examined by proton magnetic resonance imaging (MRI) at 0.5 T. An extensive protocol was used to facilitate a comparison of the efficacy of different pulse techniques. Results were also compared in 39 cases with high-resolution x-ray computed tomography (CT). MRI revealed characteristic abnormalities in each case, whereas CT was positive in only 15 of 33 patients. Milder grades 1 and 2 disease were usually undetected by CT, and in all cases, the abnormalities noted on MRI were much more extensive than on CT. Cerebral abnormalities were best shown with the T2-weighted spin-echo sequence (TE/TR = 120/1000); brainstem lesions were best defined on the inversion-recovery sequence (TE/TI/TR = 30/400/1250). Increasing TE to 120 msec and TR to 2000 msec heightened the contrast between normal and abnormal white matter. However, the signal intensity of cerebrospinal fluid with this pulse technique obscured some abnormalities.

Adult↗

Diagnosis of acute ischaemic stroke with fluid-attenuated inversion recovery and diffusion-weighted sequences.

We evaluated the feasibility and use of diffusion-weighted and fluid-attenuated inversion-recovery pulse sequences performed as an emergency for patients with acute ischaemic stroke. A 5-min MRI session was designed as an emergency diagnostic procedure for patients admitted with suspected acute ischaemic stroke. We reviewed routine clinical implementation of the procedure, and its sensitivity and specificity for acute ischaemic stroke over the first 8 months. We imaged 91 patients (80 min to 48 h following the onset of stroke). Clinical deficit had resolved in less than 3 h in 15 patients, and the remaining 76 were classified as stroke (59) or stroke-like (17) after hospital discharge. Sensitivity of MRI for acute ischaemic stroke was 98%, specificity 100%. MRI provided an immediate and accurate picture of the number, site, size and age of ischaemic lesions in stroke and simplified diagnosis in stroke-like episodes. The feasibility and high diagnostic accuracy of emergency MRI in acute stroke strongly support its routine use in a stroke centre.

Adult↗

MRI lesion volume measurement in multiple sclerosis and its correlation with disability: a comparison of fast fluid attenuated inversion recovery (fFLAIR) and spin echo sequences.

OBJECTIVES: To assess whether multiple sclerosis lesion volume measurements derived using the fast fluid attenuated inversion recovery (fFLAIR) sequence show better reproducibility or correlation with disability than those derived using the conventional spin echo (CSE) sequence. METHODS: Part I: twenty five patients with multiple sclerosis were scanned with CSE, fast spin echo (FSE), and fFLAIR. Lesion volume was determined twice for each sequence using a local threshold segmentation technique. Part II: fifty six patients with multiple sclerosis were scanned with CSE and fFLAIR. Total and regional brain lesion volumes were compared with the Kurtzke extended disability scale (EDSS) and functional systems scores (FSS). RESULTS: Part I: analysis times were significantly longer for CSE than for FSE or fFLAIR. There was no significant difference in the reproducibility of the three sequences. Part II: total lesion volumes were similar but posterior fossa lesion volumes were significantly greater for CSE and subcortical lesion volumes significantly greater for fFLAIR. There was a significant correlation between total volume and EDSS with both sequences (CSE r=0.49; fFLAIR r=0.44). Correlations for the two sequences showed minor differences when anatomical region and FSS were considered separately. CONCLUSIONS: CSE, FSE, and fFLAIR are equally reproducible; FSE yields lower volumes than CSE; fFLAIR gives similar volumes to CSE but underscores the posterior fossa. Overall clinical correlations are similar for CSE and fFLAIR.

Adult↗

[Comparative evaluation of the SPIR sequence with gadolinium and other sequences in bone diseases].

In order to assess the value of the SPIR (Spectral Presaturation with Inversion Recovery) sequence (a fat-suppression technique) with Gd-DTPA in the investigation of skeletal diseases, 50 patients were examined with conventional SE T1- and T2-weighted sequences, as well as with SE T1 and SPIR sequences after the i.v. injection of Gd-DTPA. Twenty patients were affected with a skeletal infection (11 spondylodiscites and 9 osteomyelitis) and 5 with a primary tumor; 15 had metastases and 10 a hemolymphopoietic disorder (6 myelomas and 4 non-Hodgkin's lymphomas). In the four groups of patients, the mean visibility of skeletal lesions was higher on SPIR images with Gd-DTPA than on the other images, even though a statistically significant difference was observed only in the group of infections (p < 0.002) and in myelomas and lymphomas (p < 0.001). In 13 cases with extraosseous spread, visibility was higher on contrast-SPIR images than on the other sequences, even though high sensitivity was also exhibited by SE T2-weighted sequences. Even though the SPIR sequence still exhibits some technical limitations, our study assesses the value of this sequences with Gd-DTPA in the investigation of skeletal lesions. The major advantages of contrast-SPIR imaging follow: 1) it shows skeletal lesions, which are isointense on enhanced SE T1-weighted images, 2) it provides better visibility of the lesion than the other sequences, more accurately defining their borders, 3) it provides better anatomical detailing than SE T2-weighted images and 4) its sensitivity is higher.

Adult↗

Performance in Luria's fist-edge-palm test according to educational level.

OBJECTIVE: To investigate the performance of a large population with heterogeneous educational background in a test apparently uninfluenced by formal education. METHODS: We administered the Luria's fist-edge-palm test to 966 elderly individuals (299 illiterates) while screening for dementia in a Brazilian population. Individuals with scores in the Mini-Mental State Examination below the 25th percentile (adjusted for each of 4 educational levels) were considered suspect for dementia and excluded. The influence of educational level, age, and gender on the occurrence of failures and on the number of demonstrations for a successful reproduction was investigated. RESULTS: The final population comprised 745 individuals (238 illiterates). Forty-eight individuals (25 illiterates) were unable to reproduce the sequence. Logistic regression showed that illiteracy was associated with failure, whereas gender and age were not. The proportion of individuals failing to reproduce the sequence was inversely related to the years of schooling. For those individuals who were able to reproduce the sequence, the number of demonstrations for successful reproduction was also inversely related to the years of schooling. CONCLUSION: Illiteracy and low educational level are associated with impaired performance in the fist-edge-palm test, which may be the result of the use of different strategies according to educational level.

Age Factors↗

Magnetic resonance imaging of the uterus at an ultra low (0.02 T) magnetic field.

In vivo pelvic imaging of 39 women and in vitro relaxation time measurements of four uterine specimens were performed using an ultra low field (0.02 T) MRI unit. Average T1 times measured in vitro at 37 degrees C for the myometrium and endometrium were 206 ms (SD 47 ms) and 389 ms (SD 21 ms), respectively. Corresponding T2 times were 95 ms (SD 20 ms) and 167 ms (SD 13 ms). The proton relaxation of almost all myometrial specimens proved to be biexponential, but of all endometrial specimens was monoexponential. Contrast measurements between endometrium versus myometrium and myometrium versus the junctional zone were performed after imaging 18 volunteer women using different pulse sequence parameters. Normal uterine structures were optimally demonstrated by SE 700/70. Relatively short repetition times could be used, because spin-lattice relaxation times were short at the low magnetic field. Consequently, the short repetition times allowed averaging of four excitations to create adequate images within an acceptable scanning time. In addition to T2-weighted images a T1-weighted inversion recovery sequence with a short inversion time of 50 ms (IR 1000/50/40) adequately differentiated the three uterine zones. Although pathologic lesions of the uterus including leiomyomas, anomalies and carcinomas were well demonstrated, especially with the T2-weighted spin echo pulse sequence, further investigations are needed to evaluate the optimal technique for ultra low field MR imaging of uterine tumors.

Adenocarcinoma↗

The effect of paramagnetic contrast media on T1 relaxation times in brain tumors.

PURPOSE: To study T1 relaxation times in brain tumors before and after paramagnetic contrast medium injection. MATERIAL AND METHODS: Seventeen patients with a known or suspected brain tumor were studied with an echo planar inversion recovery imaging sequence using 10 different inversion times. Double injections of Gd chelate (0.1 mmol/kg + 0.2 mmol/kg) were administered in 5 patients, and a single 0.2-mmol/kg dose in 12 patients. RESULTS: After the 0.2-mmol/kg dose, T1 decreased from 1121 +/- 130 ms to 987 +/- 103 ms in gray matter (p < 0.001), and from 666 +/- 29 ms to 646 +/- 27 ms in white matter (p < 0.001). Tumor T1 shortened from 1515 +/- 319 ms to 717 +/- 383 ms. After the 0.1-mmol/kg dose (n = 5), tumor T1 decreased from 1116 +/- 261 ms to 793 +/- 202 ms and after the additional 0.2-mmol/kg dose it decreased further to 526 +/- 141 ms. CONCLUSION: Postcontrast T1 relaxation times in tumors showed considerable variation and remained, on average, relatively long compared to white matter. This should be taken into account when deciding which pulse sequences, imaging parameters, and contrast agent doses are optimal for brain tumor imaging.

Adult↗

Fluid-attenuated inversion recovery MR imaging: identification of protein concentration thresholds for CSF hyperintensity.

OBJECTIVE: Using human volunteers and phantoms emulating CSF, we analyzed the effects of varying protein concentration on the signal intensity of saline solution. Also, for different fluid-attenuated inversion recovery (FLAIR) sequences, we compared protein concentration thresholds above which the signal from these solutions becomes hyperintense to that from brain parenchyma. SUBJECTS AND METHODS: Nine albumin solutions of varying concentrations (3.9 mg/dl to 2500 mg/dl) were imaged using fast FLAIR MR sequences (TR, 6000 msec: inversion time, 1730 msec: echo train length, 20) at different effective TEs (110, 150, 200, and 250 signal-to-noise ratios from the different albumin solutions versus albumin concentration were generated and correlated with average signal-to-noise ratios from brain parenchyma and CSF. RESULTS: We saw a gradual increase in signal-to-noise ratios from the albumin solutions as a function of albumin concentration. As the effective TE increased, the point of intersection between the plots and the average signal-to-noise ratio from brain parenchyma occurred at lower albumin concentrations. CONCLUSION: FLAIR MR imaging is potentially useful to evaluate pathologic conditions that increase CSF protein concentration. Using phantoms and healthy volunteers, we defined a protein concentration threshold above which the signal from saline solutions becomes hyperintense to that from brain parenchyma. This threshold depends on the effective TE used in the FLAIR sequence and is 250 mg/dl for an effective TE of 110 msec, 125 mg/dl for 150 msec. 110 mg/dl for 200 msec, and 95 mg/dl for 250 msec.

Adult↗

[The STIR sequence. Comparison with other MRI sequences and scintigraphy in detecting spinal metastases].

A prospective MRI study of the spine comparing short inversion-recovery sequences (STIR)-one the features of which is to potentiate the contrast of both long T1 and T2 sequences-with other spin echo and/or gradient echo MRI sequences, was conducted in 20 patients with suspected vertebral metastases. The features of the signal on STIR sequences were initially defined in 14 healthy volunteers. In the patients, the various MRI sequences were also compared to each other and to standard x-rays and bone scans. The sensitivity of detection of vertebral metastases did not appear to be significantly different between T1 sequences and the STIR sequence. However, these two sequences appeared to be significantly more sensitive than T2-weighted sequences. The STIR sequences therefore appears to be a logical complement to T1-weighted sequences in the detection of vertebral secondaries. This sequence even appears to be superior in the following situations: investigation of the cervical vertebrae, follow-up of irradiated bone, early detection of periduritis and lesions of the posterior arch.

Adult↗

[Object analysis of bone marrow MR imaging using double echo STIR sequence in hematological diseases].

The bone marrow of 84 patients with hematological disorders was investigated using short inversion time inversion recovery sequence (STIR) on an 1.5 Tesla superconducting MRI system. Double echo times of 20 and 100msec were applied to research the signal characteristics of the lesion and carry out quantitative analysis of the receiver operating characteristic curve (ROC). The hematological diseases included 19 cases of myelodysplastic syndrome (MDS), 18 of multiple myeloma (MM), 18 of chronic myelocytic leukemia (CML), 9 of aplastic anemia (AA), 8 of acute myelocytic leukemia (AML), 3 of chronic lymphocytic leukemia (CLL), 3 of myelofibrosis, and 3 others. Using STIR with double echo times, bone marrow showed high signal intensity (SI) on short TE and low SI on long TE in MDS and CML; high SI on short and long TE in myelofibrosis and CLL; high SI on short TE and high to moderately high SI on long TE in MM; and low SI on short and long TE in AA. Quantitative analysis of 33 patients showed high sensitivity and specificity in AA (81% and 94%, respectively) and moderate sensitivity and high specificity in MM (61%, 88%). CML and MDS were similar with low sensitivities (40%, 41%) and high specificities (80%, 78%). Differential diagnosis between CML and MDS was difficult using STIR with the double echo time method.

Adolescent↗

Initial feasibility studies using single-shot EPI for the detection of focal liver lesions.

Echo planar MR imaging (EPI) has been developed to completely eliminate motion artifacts and is currently being prepared for implementation into clinical MR systems. Thus, the purpose of this study was to evaluate the clinical utility of EPI in the detection of focal liver lesions and to compare EPI with in the detection of focal liver lesions and to compare EPI with contrast-enhanced CT. EPI studies were performed on an experimental 1.0 Tesla whole body system using fat-suppressed single-shot spin echo (SE) and inversion recovery (IR) pulse sequences. A total of 26 liver tumors in 12 patients scheduled for liver resection were prospectively examined and correlated with intraoperative ultrasound, surgery, and pathology as the gold standard. Quantitative analysis of EPI was performed by means of liver signal-to-noise and tumor-liver contrast-to-noise calculations. Diagnostic performance compared with contrast-enhanced CT was assessed by means of ROC analysis. Lesion-liver contrast was highest with EPI SE at a TE-time of 70 ms and this technique showed best lesion detectability as measured by area under curve (AUC) values. Among EPI techniques, the IR sequence with an inversion time of 300 ms to null the liver signal showed high lesion-liver contrast but all four reviewers reported problems assessing liver anatomy. Improved EPI techniques may prove useful for screening of focal liver lesions.

Adult↗

High-resolution MR imaging of the elbow using a microscopy surface coil and a clinical 1.5 T MR machine: preliminary results.

OBJECTIVE: To obtain high-resolution MR images of the elbow using a microscopy surface coil with a 1.5 T clinical machine and to evaluate the feasibility of its use for elbow injuries. DESIGN AND PATIENTS: Five asymptomatic normal volunteers and 13 patients with elbow pain were prospectively studied with MR imaging using a microscopy surface coil 47 mm in diameter. High-resolution MR images using a microscopy coil were obtained with fast spin echo (FSE) proton density-weighted sequence, gradient recalled echo (GRE) T2*-weighted sequence, and short tau inversion recovery (STIR) sequence, with a 1-2 mm slice thickness, a 50-70 mm field of view, an imaging matrix of 140-224 x 512 using zero fill interpolation, and 2-6 excitations. RESULTS: High-resolution MR images of normal volunteers using a microscopy coil clearly showed each structure of the medial and lateral collateral ligaments on GRE T2*-weighted images and FSE proton-density weighted images. Partial medial collateral ligament injury, a small avulsion of the medial epicondyle, and osteochondritis dissecans were well demonstrated on high-resolution MR images. CONCLUSION: High-resolution MR imaging of the elbow using a microscopy surface coil with a 1.5 T clinical machine is a promising method for accurately characterizing the normal anatomy of the elbow and depicting its lesions in detail.

Adolescent↗

Assessment of posterior fossa damage in MS using MRI.

In multiple sclerosis (MS), brain stem and cerebellum are frequent sites of damage in clinically isolated syndromes at presentation and it is likely that lesions located in such structures can have an important impact on the development of disability in the definite forms of the disease. In patients presented with isolated brain stem syndromes, the symptomatic lesion was often not detected by magnetic resonance (MR) imaging. But patients with asymptomatic infratentorial lesions progressed to clinically definite MS in 65% of cases. Infratentorial lesions are included in various MR criteria designed to assist in the differential diagnosis of MS lesions from incidental lesions, to differentiate MS from subcortical encephalopathic arteriopathy. The preferred MR sequence to visualize infratentorial lesions is the fast spin echo sequence. It is preferred to conventional spin echo and fast fluid attenuated inversion recovery sequences because of its relatively short acquisition time and good sensitivity. The correlation between disability and infratentorial lesion load on T2 weighted sequences is controversial. However, it was recently shown that the correlations between clinical measures and T1 lesion load, histogram magnetization transfer ratio and peak positions, and infratentorial volume measurements are strong. These findings suggest that one of the major factors in the development of disability in patients with MS is the pathological damage in clinically eloquent sites such as the brain stem and cerebellum.

Brain Diseases↗

MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: a study on inter-observer agreement.

According to the current WHO criteria, technical investigations included in the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) are electroencephalogram (EEG) and CSF-analysis for 14-3-3 proteins. MRI is not a criterion for the diagnosis of sCJD, although typical changes have been described. We investigated the reliability of MRI in the sCJD diagnosis, evaluated MRI sequences and compared MRI with EEG and 14-3-3. This study includes 193 consecutive suspected sCJD patients who had been referred to the German CJD Surveillance Unit from 2001 to 2003. Three observers independently analysed MRI scans, blinded to clinical data. MRI was rated as 'typical for sCJD' if increased signal intensity was detected in the caudate nucleus and putamen. We analysed 442 MRI scans [184 T2-weighted sequences, 132 fluid attenuated inversion recovery (FLAIR) sequences, 75 diffusion-weighted sequences and 51 proton-density weighted sequences]. Inter-observer agreement was 123 of 193 patients or 63.7% (overall kappa = 0.53). Sensitivity of MRI in clinically probable or autopsy-proven sCJD was 59.7% for Observer 1, 58.3% for Observer 2 and 70.8% for Observer 3; specificity was high (84.2, 89.5 and 81.6%, respectively). Diffusion-weighted sequences best showed the pathologic changes, followed by FLAIR. Periodic sharp and slow wave complexes were detected in the EEG in 32% (sensitivity), the 14-3-3 proteins in CSF were elevated in 91%. We conclude that the detection of hyperintense basal ganglia in MRI helps to improve the clinical diagnosis, and therefore, we propose to incorporate MRI in the diagnostic criteria for sCJD.

14-3-3 Proteins↗

Imaging the changes in renal T1 induced by the inhalation of pure oxygen: a feasibility study.

The effect of the inhalation of pure oxygen on the kidney was evaluated by measuring monoexponential T1 and T2* relaxation times in nine volunteers using a multiple-shot turbo spin echo and multiple echo gradient echo sequences, respectively. The T1 of the renal cortex decreased significantly when breathing pure oxygen as compared to normoxia (from 882 +/- 59 to 829 +/- 70 msec, P < 0.05), while that of the renal medulla was unchanged. No significant changes were seen in the T2* of either compartment. Dynamic imaging using an inversion recovery sequence with an optimized inversion time typically produced signal changes of 20% in the renal cortex. Studies to assess if oxygen-induced changes in flow contributed to this effect showed that the flow contribution was not significant. Although longer inversion times (880 ms) produced optimal contrast, acceptable contrast was also obtained at shorter inversion times (450 msec) in the renal cortex, spleen, and lung, with the latter being of opposite polarity to the other two tissues, implying a shorter parenchymal T1 than previously reported in the literature. The results are consistent with oxygen acting as an intravascular contrast agent which induces a shortening of T1 in the arterial blood volume.

Feasibility Studies↗