MR imaging of pelvic lymph nodes in primary pelvic carcinoma with ultrasmall superparamagnetic iron oxide (Combidex): preliminary observations

The potential of ultrasmall superparamagnetic iron oxide (Combidex)-enhanced MRI of pelvic lymph nodes in patients with primary pelvic carcinoma is evaluated. Fifteen histologically classified lymph nodes in six patients with known primary pelvic cancer (four prostate; one rectum; one uterus) were evaluated with T2-weighted fast spin-echo (FSE) and T2*-weighted gradient-echo (GRE) MRI at 1.5T 12 to 48 hours after intravenous administration of Combidex at a dose of 1.7 mg Fe/kg. Quantitative image evaluation was performed by comparing signal intensity of individual nodes on pre- and postcontrast images. All patients proceeded to pelvic lymph-node biopsy or surgical dissection, where six were found to be benign and nine were malignant. Of the 15 lymph nodes, four nodes showed a decrease in signal intensity. Of these, three, in which signal loss was homogenous were benign, and one, in which the signal-intensity decrease was heterogeneous, was malignant (micrometastases). No signal change was noted in 11 of 15 lymph nodes of which three were benign (inflammatory) and eight were malignant. Combidex is a promising MR contrast agent for evaluating pelvic lymph nodes. Our preliminary observations suggest that the agent is most useful for classifying normal lymph nodes.     

Hypersignal of the intervertebral disks in T1-weighted spin-echo MRI sequences

In magnetic resonance imaging, when there is calcification of the intervertebral disk, signals usually become weaker in all the sequences. Exceptionally, a spontaneous hypersignal is obtained in T1 weighted spin-echo sequences. We report 4 cases of spontaneous hypersignals from disks in T1 weighted spin-echo sequences. In 3 cases, calcifications were visualized with conventional radiology or computed tomography. In 1 case, there was no calcification of the disk, but its density, compared with adjacent disks, was 20 HU greater, suggesting inframacroscopic calcification.     

Assessment of T2- and T1-weighted MRI brain lesion load in patients with subcortical vascular encephalopathy

Previous cross-sectional studies in patients with subcortical vascular encephalopathy (SVE) have shown little or no correlation between brain lesion load and clinical disability, which could be due to the low specificity of T2-weighted MRI. Recent studies have indicated that T1-weighted MRI may be more specific than T2-weighted MRI for severe tissue destruction. We studied 37 patients with a diagnosis of SVE and 11 normal controls with standardised T1- and T2-weighted MRI. All patients underwent detailed clinical assessment including a neuropsychological test battery and computerised gait analysis. Both the T2- and T1-weighted total MRI lesion loads different between patients and controls different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in controls than in patients. There was no overall correlation of T1- or T2-weighted lesion load with clinical disability, but group comparison of patients with severe and mild clinical deficits showed different lesion loads. We suggest that T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality in patients with SVE.     

New pulse sequences for T1- and T1/T2-contrast enhancing in NMR imaging

Improved pulse sequences DIFN (abbreviation of the words: DIFferentiation by N pulses), 90 degrees - tau1 - 180 degrees tau1 - . . . 180 degrees - tau1 with optimised time intervals tau1- for T1 measurement and contrast enhancing in NMR imaging are presented. The pulse sequences DIFN have a better sensitivity to T1 than the well-known pulse sequence SR. In contrast to the IR pulse sequence, the information given by the DIFN pulse sequence is more reliable, because the NMR signal does not change its sign. For a given time interval tau0 < or = (0.1 - 0.3) T(1) the DIFN pulse sequences serve as T1-filters. They pass the signal components with relatively short T1 < T(1) and suppress the components with relatively long T1 < T(1). The effects of the radiofrequency field inhomogeneity and inaccurate adjusting of pulse lengths are also considered. It is also proposed in this work to use the joint T1T2-contrast in NMR imaging obtained as a result of applying the DIFN pulse sequences in combination with the well-known Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence. The region of interest, where the contrast should be especially enhanced, is specified by the two times at which measurements are performed, which allow the amplitudes of pixels to reach some defined levels by spin-lattice and spin-spin relaxation.     

Malignant lesions of the liver identified on T1- but not T2-weighted MR images at 1.5 T

The authors reviewed their 2 1/2-year experience with a magnetic resonance (MR) imaging protocol for a 1.5-T MR imager that included T2-weighted fat-suppressed spin-echo, T1-weighted breath-hold gradient-echo, and serial dynamic gadolinium-enhanced T1-weighted gradient-echo imaging to identify histologic types of malignant liver lesions more apparent on T1- than on T2-weighted images. MR images of 212 consecutive patients with malignant liver lesions were reviewed. T2-weighted, T1-weighted, and dynamic contrast-enhanced T1-weighted images were examined separately in a blinded fashion. Seven patients demonstrated liver lesions (lymphoma [two patients] and carcinoid, hepatocellular carcinoma, colon adenocarcinoma, transitional cell carcinoma, and melanoma [one patient each]) on T1-weighted images that were inconspicuous on T2-weighted images. In all cases, the lesions were most conspicuous on T1-weighted images obtained immediately after administration of contrast agent. Histologic confirmation was present for all seven patients. The consistent feature among these lesions was that they were hypovascular, due either to a fibrous stroma or to dense monoclonal cellularity. These results suggest that in some patients with hypovascular primary neoplasms, the lesions may be identified only on T1-weighted images, and that immediate postcontrast T1-weighted images are of particular value in demonstrating lesions.     

Comparison of in-phase and opposed-phase GRE and conventional SE MR pulse sequences in T1-weighted imaging of liver lesions

PURPOSE: Our goal was to compare in-phase (IP) and opposed-phase (OP) GRE and conventional SE sequences in T1-weighted (T1-W) imaging of the liver and to evaluate chemical shift GRE imaging in characterizing liver/lesions for fat content. METHOD: IP and OP T1-W GRE with fast low angle shot (FLASH) technique and T1-W SE sequences were compared in 162 patients at 1.0 T. Chemical shift GRE imaging was used to characterize lesions with fat content. Two hundred sixteen lesions were analyzed in three groups of liver: (a) "normal" liver (n = 74 with 110 lesions); (b) cirrhotic liver (n = 76 with 85 lesions); and (c) fatty liver (n = 12 with 21 lesions). Liver/lesion contrast and liver/lesion contrast-to-noise ratio were assessed for lesion detectability. The percentage of signal intensity variation (SIV) between IP and OP images was used to characterize lesions for fat content. RESULTS: The OP GRE sequence had significantly higher contrast for normal and cirrhotic livers (p < 0.001), and the IP GRE sequence had significantly higher contrast and contrast-to-noise ratio for fatty liver (p < 0.001). There were no significant differences between OP, IP, and T1-W SE imaging in cirrhotic cases for contrast-to-noise ratio (p < 0.28). Chemical shift imaging detected fat in 21 lesions (9.7%, mean SIV, 191.1%) (sensitivity and specificity 100% when compared with fine needle aspiration cytology). CONCLUSION: OP GRE sequences could replace conventional SE sequences in T1-W imaging in nonfatty livers, whereas in fatty livers, T1-W SE sequences could be obviated, but both OP and IP sequences are necessary. Chemical shift imaging (OP and IP) can be used to accurately characterize lesions for fat content.     

T2-weighted breath-hold MRI of the liver at 1.0 T: comparison of turbo spin-echo and HASTE sequences with and without fat suppression

To compare the clinical usefulness of T2-weighted breath-hold sequences for imaging the liver, 33 patients with 97 focal hepatic lesions were studied with a 1.0-T scanner by using T2-weighted breath-hold turbo spin-echo (SE) sequences and T2-weighted breath-hold half-Fourier single-shot turbo SE (HASTE) sequences with and without fat suppression. Images were quantitatively analyzed for liver signal-to-noise ratio (SNR) and lesion-to-liver contrast-to-noise ratios (CNR). Qualitative analysis was performed for lesion conspicuity, motion artifacts, and anatomic sharpness of extrahepatic structures. Breath-hold turbo SE imaging with fat suppression showed the highest CNR for cystic lesions and the best lesion conspicuity for cystic and solid lesions among the four sequences. For solid lesions, there was no significant difference of lesion-to-liver CNR between them. HASTE sequence was superior to turbo SE sequences in terms of motion artifacts; however, the usefulness for evaluating focal hepatic lesions was limited compared with turbo SE sequence with fat suppression. Addition of fat suppression was not helpful for HASTE imaging because of decreased lesion conspicuity and extrahepatic details without the advantage of reducing motion artifacts. This study suggests that turbo SE sequence with fat suppression is most useful for breath-hold T2-weighted liver imaging at 1.0 T. Addition of imaging without fat suppression can be considered for evaluating extrahepatic structures. HASTE sequence may have a role for imaging uncooperative patients due to absence of motion artifacts.     

Comparison of ultrafast half-Fourier single-shot turbo spin-echo sequence with turbo spin-echo sequences for T2-weighted imaging of the female pelvis

1. This investigation was undertaken to compare pre- and postjunctional receptors involved in the responses of the canine mesenteric and pulmonary arteries to angiotensin II. 2. In the mesenteric artery, angiotensin II caused an enhancement of tritium overflow evoked by electrical stimulation (EC30% = 5 nM), the maximal effect representing an increase by about 45%. Postjunctionally, angiotensin II caused concentration-dependent contractions (pD2 = 8.57). Saralasin antagonized both pre- and postjunctional effects of angiotensin II, but it was more potent at post- than at prejunctional level (pA2 of 9.51 and 8.15, respectively), while losartan antagonized exclusively the postjunctional effects of angiotensin II (pA = 8.15). PD123319 had no antagonist effect either pre- or postjunctionally. 3. In the pulmonary artery, angiotensin II also caused an enhancement of the electrically-evoked tritium overflow (EC30% = 1.54 nM), its maximal effect increasing tritium overflow by about 80%. Postjunctionally, angiotensin II caused contractile responses (pD2 = 8.52). As in the mesenteric artery, saralasin antagonized angiotensin II effects at both pre- and postjunctional level and it was more potent postjunctionally (pA2 of 9.58 and 8.10, respectively). Losartan antagonized only the postjunctional effects of angiotensin II (pA2 = 7.96) and PD123319 was ineffective. 4. It is concluded that in both vessels: (1) pre- and postjunctional receptors belong to a different subtype, since they are differently antagonized by the same antagonists; (2) postjunctional receptors belong to AT1 subtype, since they are blocked by losartan but not by AT2 antagonists; (3) prejunctional receptors apparently belong to neither AT1 or AT2 subtype since they are blocked by neither AT1 nor AT2 antagonists.     

Studies on utility of MR T2-weighted images using multishot echo-planar imaging for hepatic mass lesions

MR T2-weighted images using multishot echo-planar imaging (EPI) and fast spin-echo (FSE) sequences were obtained in 22 patients with hepatic masses. Multishot EPI sequences included eight-shot breath-hold EPI and 16-shot EPI without breath-hold, while FSE sequences included nonfat-suppressed respiratory-triggered FSE, fat-suppressed respiratory-triggered FSE, and nonfat-suppressed breath-hold FSE. Signal-to-noise ratio, contrast-to-noise ratio and artifacts were compared between EPI and FSE images of 47 hepatic masses. In evaluating solid tumors, EPI provided image quality equal or superior to that of FSE, whereas in the evaluation of nonsolid tumors FSE showed better image quality than EPI. In conclusion, it was demonstrated that in the evaluation of hepatic solid tumors T2-weighted eight-shot breath-hold EPI can replace both nonfat-suppressed respiratory-triggered FSE and breath-hold FSE, and it was suggested that eight-shot breath-hold EPI can replace fat-suppressed respiratory-triggered FSE to reduce patient discomfort and increase examination throughput.     

Comparison of turbo inversion recovery magnitude (TIRM) with T2-weighted turbo spin-echo and T1-weighted spin-echo MR imaging in the early diagnosis of acute osteomyelitis in children

OBJECTIVE: To compare turbo inversion recovery magnitude (TIRM) with standard T1-weighted (T1-W) and T2-weighted (T2-W) MR sequences in the very early detection of acute osteomyelitis in children. MATERIALS AND METHODS: In 15 children with osteomyelitis, 15 sets of T1-W spin-echo (SE) (TR/TE, 400-640/12-17), T2-W turbo spin-echo (TSE) (TR/TE/ETL, 3290-4465/112-120/11), and TIRM (TR/TE/TI, 4000-6120/60/160) images were acquired with a 1.0-T magnet. Contrast-to-noise (C/N) ratios and percentage of signal between lesion and normal bone marrow were analysed with a computer-assisted image analysing system in a region of interest (ROI). RESULTS: In 13 of 15 patients, the absolute signal enhancement in a ROI on the TIRM images was better than on the T1-W SE and T2-W TSE images and in 14 of 15 cases, C/N ratios were also better on the TIRM images than on the other sequences. In the other cases, the TIRM signal was diagnostically equivalent. On the TIRM images, the signal difference between normal and pathological tissue was increased to 43-281% (mean 124%). On the T2-W TSE images, this signal difference was 4-79% (mean 36%) and on the T1-W SE images 6-77% (mean 37%). Conclusion. The TIRM sequence is highly sensitive for detecting bone marrow oedema in the very early stage of acute osteomyelitis in children. MRI utilising the TIRM sequence allowed for an early diagnosis. With scan time of less than 4 minutes, this sequence is superior to T1-W SE and T2-W TSE images for detecting early osteomyelitis-associated bone marrow oedema.     

Translational regulation of mRNAs with distinct IRE sequences by iron regulatory proteins 1 and 2

Iron regulatory proteins 1 and 2 (IRP-1, IRP-2) interact with iron-responsive elements (IREs) present in the 5'- or 3'-untranslated regions (UTR) of several mRNAs coding for proteins in iron metabolism. Whereas binding of IRP-1 and -2 to an IRE in the 5'-UTR inhibits mRNA translation in vitro, it has remained unknown whether either endogenous protein is sufficient to control translation in mammalian cells. We analyzed this question by taking advantage of published mutant IREs that are exclusively recognized by either IRP-1 or IRP-2 in vitro. These IREs were inserted into the 5'-UTR of a human growth hormone reporter mRNA, and translational regulation was measured in stably transfected mouse L cells. Cells cultured in iron-rich or -depleted medium were labeled with [35S]methionine, and secreted growth hormone was immunoprecipitated. IREs with loop sequence specific for IRP-1 (UAGUAC), IRP-2 (CCGAGC), or both proteins (GAGUCG and the wild-type CAGUGC sequence) all mediated translational regulation, in contrast to a control sequence (GCUCCG) that binds neither IRP-1 nor IRP-2. Control experiments excluded IRP-1 binding to the IRP-2-specific sequence in vivo. The present data demonstrate that IRP-1 and IRP-2 can independently function as translational repressors in living cells.     

Differentiation between hepatic cavernous hemangioma and malignant tumor with T2-weighted MRI: comparison of fast spin-echo and breathhold fast spin-echo pulse sequences

An in vitro jaw-attached brainstem preparation was developed to investigate the relationship between jaw opener and closer muscle activity during chemically induced rhythmical jaw movements in neonatal rats. In the majority of preparations examined, where a defined region of brainstem was isolated and the neuronal innervation of the jaw opener and closer muscles was left intact, bath application of the excitatory amino acid agonist N-methyl-D,L-aspartate (NMA, 20-40 microM) in combination with bicuculline (BIC 10 microM), a GABA(A) antagonist, produced rhythmical electromyogram (EMG) activity in jaw opener and closer muscles, bilaterally, in conjunction with rhythmical jaw movements. Low concentrations of NMA (20 microM) in combination with BIC produced temporally coordinated activity between the jaw opener and closer muscles, ipsilaterally. With higher doses of NMA (40 microM), each muscle group exhibited bursting, but temporal coordination between them was difficult to establish. Similarly, NMA application in combination with the glycine antagonist strychnine (STR, 10 microM), also produced rhythmical EMG activity from both opener and closer muscles, ipsilaterally, but showed no temporal coordination between the antagonist muscle pair. However, coordination of opener and closer muscle discharge could be restored by the addition of BIC to the bath. We suggest that there exist separate, but coordinated, rhythm generator circuits for opener and closer motoneuronal discharge located in close proximity to the trigeminal motor nucleus and under GABAergic control for production of temporal coordination between rhythmogenic circuits.     

Hepatic T2-weighted MRI: a prospective comparison of sequences, including breath-hold, half-Fourier turbo spin echo (HASTE)

The purpose of this study was to quantitatively compare the hepatic contrast characteristics of conventional spin-echo (CSE) and fast spin-echo (FSE) sequences with breath-hold T2-weighted images acquired with half-Fourier turbo spin echo (HASTE). Forty-five patients were examined with a phased-array surface coil. Nineteen patients had focal hepatic lesions, including eight malignant tumors, 10 cavernous hemangiomas, and one hepatic adenoma. Twenty-six patients had no focal hepatic lesions. T2-weighted images with comparable TE were acquired with CSE, FSE, and HASTE pulse sequences. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for liver, spleen, and lesions were measured. FSE demonstrated significantly better quantitative performance than CSE for liver-spleen CNR (P .0084). No statistically significant difference was demonstrated between FSE and CSE for liver or spleen SNR. FSE demonstrated clear scan time and resolution advantages over CSE. HASTE performed significantly poorer than CSE and FSE for liver-spleen CNR (P < .0001), liver SNR (P = .0002 for CSE and P < .0001 for FSE), and spleen SNR (P < .0001). Optimized FSE images with a short echo train length performed comparably to CSE images of equivalent TE. Liver-lesion CNR was suppressed on HASTE images, suggesting that long echo train length FSE sequences could diminish solid lesion detection compared to CSE and short echo train length FSE.     

The membrane association sequences of the prostaglandin endoperoxide synthases-1 and -2 isozymes

Based on the crystal structures of the prostaglandin endoperoxide H synthases-1 and -2 (PGHS-1 and PGHS-2), four short amphipathic helices near the amino termini of these proteins have been proposed to act as membrane binding domains. We constructed a series of plasmids coding for amino-terminal sequences of the PGHS-1 and PGHS-2 joined to the green fluorescent protein from Aequorea victoria, and we examined the subcellular distribution of the fusion proteins expressed from these plasmids using confocal microscopy of intact cells and Western blot analysis. DNA sequences coding for amino acids 1-139 and 1-136 of PGHS-1 and PGHS-2, respectively, which include the signal peptides, epidermal growth factor homology domains, glycosylation sites, and the putative membrane-binding helices of these two isozymes, were required for targeting the PGHS-green fluorescent protein fusion proteins to the endoplasmic reticulum and nuclear membranes when expressed in NIH 3T3 cells. Chimeric proteins that did not contain the putative membrane binding domains are targeted to the endoplasmic reticulum, but are not associated with membrane structures, and are present only in soluble cell fractions. These are the first experiments to directly confirm that the amphipathic helices present near the amino terminus of the PGHS-1 and PGHS-2 isozymes act as membrane anchors.     

Association of beta-agonists with corresponding beta 2- and beta 1-adrenergic pentapeptide sequences

Synthesized beta 1- and beta 2-pentapeptide sequences corresponding to published adrenoceptor transmembrane activation site subtypes were investigated in vitro for selectivity in association for drug ligands of known selectivity. Both nuclear magnetic resonance spectroscopy and molecular mechanics demonstrated that structural differences among the corresponding pentapeptide activation-site sequences can explain agonist selectivity. Results suggest the agonists bind across the activation site loop on the second transmembrane alpha-helix by dipole/dipole interactions between a ligand and the peptide. Since electrostatic interactions within the membrane may determine the rate of intercellular ion flux, agonist association across the activation site sequence could thereby decrease electrostatic resistance to positive ion flux into the cell. Interactions between the peptides and the ligands may provide insight into the structures and mechanisms involved in association of ligands for the identical sequences on the beta-adrenoreceptors.