Functionality and connectivity analysis by magnetic resonance imaging

Magnetic resonance (MR is a remarkably versatile technology applicable to various aspects of medical science. Currently, there are three categories of MR techniques available for probing human brain function in detail. The first category comprises the most widely utilized techniques which make use of the metabolic effects of brain activation, represented by BOLD (blood oxygenation level dependent) functional magnetic resonance imaging (fMRI). The second category of techniques deals with apparent diffusion tensor probing the axonal connectivity and is represented by three dimensional anisotropy contrast (3DAC) axonography. The third category of techniques is a biological application of classical nuclear magnetic resonance (NMR) spectroscopy capable of providing biochemical information in vivo and is represented by spectroscopic imaging (SI). As techniques directly applicable to clinical medicine, BOLD fMRI and 3DAC axonography possess the highest potential.     

Serendipity in diagnostic imaging: magnetic resonance imaging of the breast

BACKGROUND: Magnetic resonance imaging (MRI) of the breast has been proposed as a noninvasive diagnostic test for evaluation of suspicious ("index") lesions noted on mammography and/or clinical breast examination (CBE). However, women may have incidental ("serendipitous") lesions detected by MRI that are not found on mammography or CBE. To understand better whether or not biopsy procedures should be performed to evaluate serendipitous lesions, we estimated the breast cancer risk for women with this type of lesion. METHODS: A decision analysis model was used to estimate the positive predictive value (i.e., the chance that a woman with a serendipitous lesion has cancer) of MRI for serendipitous lesions in women who had an abnormal mammogram and/or CBE suspicious for cancer (where a biopsy procedure is recommended). We restricted the analysis to data from women whose index lesions were noncancerous and used meta-analysis of published medical literature to determine the likelihood ratios (measures of how test results change the probability of having cancer) for MRI and the combination of CBE and mammography. The positive predictive value of MRI was calculated using the U.S. population prevalence of cancer (derived from registry data) and the likelihood ratios of the diagnostic tests. RESULTS: Under a wide variety of assumptions, the positive predictive value of MRI was extremely low for serendipitous lesions. For instance, assuming sensitivity and specificity values for MRI of 95.6% and 68.6%, respectively, approximately four of 1000 55- to 59-year-old women with serendipitous lesions would be expected to have cancer (positive predictive value = 0.44%, 95% confidence interval = 0.24%-0.67%). CONCLUSION: In women with a suspicious lesion discovered by mammography and/or CBE that is found to be benign, serendipitous breast lesions detected by MRI are extremely unlikely to represent invasive breast cancer. Immediate biopsy of such serendipitous lesions may, therefore, not be required.     

Contrast-enhanced magnetic resonance imaging of the breast: interpretation guidelines

In the past decade, most studies have shown that in selected indications of breast imaging, the overall accuracy can be improved by the additional use of contrast-enhanced magnetic resonance imaging (MRI). The sensitivity of contrast-enhanced MRI for invasive malignancy is >98%; reported specificity, however, ranges from 37% to 97%. This range of values is predominantly caused by different patient preselection and interpretation criteria. Other factors, such as technique (e.g., choice of pulse sequence and echo time, slice thickness, reduction in artifacts, dosage of contrast agent, and methods for elimination of fat signal), hormonal influences (menstrual cycle and hormonal replacement therapy), and levels of verification, influence the accuracy and reproducibility of contrast-enhanced MRI. An appropriate application of MRI is highly desirable because of the increased costs of imaging, increased rates of biopsy due to false-positive results, and possibility of false-negative results caused by technical failures and interpretation errors. We present an overview of the sensible application and interpretation of contrast-enhanced MRI of the breast based on our experience and on published data.     

Tests for DNA and chromosomal damage induced by nuclear magnetic resonance imaging

Chinese hamster ovary (CHO) cells in culture were exposed in a nuclear magnetic resonance (NMR) imaging apparatus to a strong magnetic field, pulsed field gradients, and radio frequency emissions. No chromosomal aberrations were induced even after an exposure of approximately 14 hours. No sister chromatid exchanges were induced by four-hour exposures to either low (average 7.2 mW) or high (average 61.2 mW) radio frequency power. When HeLa cells were exposed for 16 hours to an average radio frequency power of 61.2 mW, no inhibition of DNA synthesis was detectable. These data indicate that the conditions used for NMR imaging do not cause genetic damage which is detectable by any of these methods.     

Adenoid cystic carcinoma of the breast: value of histologic grading and proliferative activity

Using vitreous fluorophotometry and quantitative fluorescence microscopy the authors studied the permeability of the blood-retinal barrier (BRB) to fluorescein in control and in 8 days streptozotocin-induced diabetic rats. Vitreous fluorophotometry showed that fluorescein permeates BRB in control and in diabetic rats. However, in diabetic rats the permeability to fluorescein was significantly increased as compared to control rats. The vitreous penetration ratio (VPR) values for total and free fluorescein at 60 min, were higher for diabetic rats (231.2+/-12.9 min-1 for total fluorescein and 1299.24+/-58.0 min-1 for free fluorescein) than for control rats (95.5+/-3.5 min-1 for total fluorescein and 646.6+/-55. 0 min-1 for free fluorescein) (P<0.05). Quantitative confocal fluorescence microscopy confirmed these findings and identified the site of leakage across the BRB by comparing the relative importance of the fluorescein leakage across the outer and inner BRB. In control rats the fluorescence levels remained relatively low in the photoreceptor layer, next to the outer BRB but in the inner nuclear layer, next to the inner BRB reached values that were almost ten times higher. These results suggest that in retinas of control rats fluorescein penetrates predominantly through the inner BRB. In diabetic rats the fluorescence levels in the photoreceptor and in the inner nuclear layer were significantly increased as compared to the fluorescence levels in controls rats. Nevertheless, in the inner nuclear layer the fluorescence levels were also generally higher than the fluorescence levels at the photoreceptor layer. The rates of fluorescence levels between the inner nuclear layer and the photoreceptor layer were apparently 3:1, 60 min after the single intravenous injection of fluorescein. Also, the fluorescein penetration in the inner nuclear layer of the diabetic rats is higher than that observed in the inner nuclear layer of the control rats (P<0.001). These findings suggest that the permeability to fluorescein of both components of the BRB is increased 8 days after the induction of diabetes by streptozotocin and that the permeability of the retinal vasculature is preferentially affected.     

Vascularity of proliferative breast disease and carcinoma in situ correlates with histological features

The level of vascularity within an invasive breast carcinoma is a predictor of metastatic potential and survival. However, little is known about the vascular potential and prognostic value of angiogenesis in preinvasive breast pathology. Women with proliferative breast disease or carcinoma in situ are at increased risk of developing invasive breast cancer. This relative risk increases in correlation with defined histopathological features. We asked whether these early proliferative lesions and carcinoma in situ were capable of inducing a vascular supply. Vascularity in preinvasive archival paraffin-embedded breast tissue from 90 patients was quantified by immunohistochemical identification of vessels using anti-von Willebrand factor. Vascular scores were analyzed with respect to histopathological diagnosis, age at diagnosis, and presence of coincident invasive disease. These data indicate that: (a) the vascularity of histopathologically normal epithelium is greater in breasts containing invasive disease than in breasts lacking invasive disease; (b) simple proliferative breast disease induces a vascular supply greater than that of normal breast epithelium; and (c) vascularity increases in proportion to epithelial lesion progression and relative risk of invasion. These studies indicate that the vascularity of preinvasive breast pathology may be a clinically useful predictor of invasive breast cancer.     

Preoperative diagnosis of primary fallopian tube carcinoma by magnetic resonance imaging: a case report

Because of the rarity and insidious onset of primary adenocarcinoma of the fallopian tube, early diagnosis is very difficult. Primary fallopian tube carcinoma is also rarely diagnosed preoperatively. This report reviews the value of magnetic resonance imaging (MRI) in aiding the detection of early-stage primary fallopian tube carcinoma in a 48-year-old female. The diagnosis was based on clinical suspicion, elevated CA-125 and MRI. MRI demonstrated the tumor as an area of solid masses with marked enhancement after gadolinium-diethylenetetraaminepentaacetic acid (Gd-DTPA) administration. Primary fallopian tube carcinoma was confirmed by pathologic examination. We hope that, with improvements in imaging, early diagnosis of such a malignant disease could become routinely possible in the future.     

Macroscopic tumor volume of malignant glioma determined by contrast-enhanced magnetic resonance imaging with and without magnetization transfer contrast

The purposes of this study were to compare the conspicuity and lesion volume of contrast-enhancing macroscopic malignant glioma determined by postcontrast magnetic resonance (MR) imaging with and without magnetization transfer (MT) saturation, and to discuss possible implications for radiotherapy planning. Nineteen patients (age 24-60 years) with histologically proven malignant glioma were prospectively examined by MR imaging. After the administration of gadolinium dimeglumine (0.1 mmol/kg body weight), the lesions were imaged with an MT-weighted FLASH (fast, low-angle shot) pulse sequence and with a conventional T1-weighted spin-echo (SE) sequence without MT saturation. The mean tumor volumes of gliomas measured on MT-weighted FLASH images were significantly (p < .01) larger than those obtained from T1-weighted SE images (45 +/- 15 cm3 vs. 33 +/- 10 cm3). The mean contrast-to-noise ratio of enhancing lesions on MT-weighted FLASH was 48 +/- 14 compared with 30 +/- 14 on SE images, representing a significant (p < .01) improvement. We conclude that the volume of contrast enhancement of malignant glioma identified on MT-weighted FLASH images represents the area of disrupted blood-brain barrier. If this volume of subtle contrast enhancement is caused by tumor infiltration and represents the boost target volume for stereotactic radiosurgery or brachytherapy, MT-weighted FLASH images would be better than T1-weighted SE images to define these volumes. These improved delineation of areas at highest risk for recurrence following radiation therapy should enhance the efficacy of treatment planning for high-boost therapy.     

Preoperative staging of rectal carcinoma by magnetic resonance imaging with a pelvic phased-array coil

BACKGROUND: The use of surface coils for magnetic resonance imaging (MRI) allows enhanced image definition and so potentially more accurate staging of colorectal cancer. Endorectal coil imaging is invasive, operator dependent and impossible in a high proportion of patients due to rectal stricture. The phased-array pelvic coil, however, is non-invasive and applicable to all rectal tumours. METHODS: A pelvic phased-array coil was used for preoperative MRI staging of 38 primary rectal carcinomas. Results were expressed according to the Dukes and tumour nodes metastasis (TNM) classifications. After resection of the tumour, the stage predicted on MRI was compared with the pathological classification. RESULTS: The overall accuracy of preoperative staging with the pelvic phased-array coil was 55 per cent for both Dukes class and T stage. Assessment of nodal involvement gave an overall accuracy for MRI of 76 per cent with a sensitivity of 57 per cent and specificity of 88 per cent. CONCLUSION: Use of a pelvic phased-array coil did not improve the staging accuracy of MRI to a clinically useful level.     

Islet cell tumors: comparison of dynamic contrast-enhanced CT and MR imaging with dynamic gadolinium enhancement and fat suppression

Ten patients with 11 islet cell tumors underwent dynamic contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging within a 1-month period. MR imaging depicted all 11 tumors, and CT depicted seven of the 11 tumors. CT did not depict four of seven tumors that measured 2.5 cm in diameter or less. Islet cell tumors had low signal intensity on T1-weighted fat-suppressed MR images, and gastrinomas were best shown with this technique. Two of three insulinomas less than 1.5 cm in diameter were best shown on dynamic contrast-enhanced fast low-angle shot (FLASH) images as uniform areas of high signal intensity. Hepatic metastases were seen in five patients and showed peripheral ringlike enhancement best demonstrated on dynamic gadolinium-enhanced FLASH images. Hepatic lesions were most conspicuous on T2-weighted fat-suppressed spin-echo images. MR imaging with dynamic gadolinium enhancement and fat suppression is a promising tool in the investigation of islet cell tumors.     

Hypertensive intra-arterial chemotherapy for endometrial carcinoma assessed by transvaginal Doppler ultrasound and magnetic resonance imaging

We examined the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using transvaginal Doppler ultrasound and magnetic resonance imaging. Angiotensin II, 100 mg cisplatin, and 40 mg doxorubicin were prescribed for 8 patients with endometrial carcinoma (3 stage Ia; 3 stage Ib; 2 stage II). The resistance index (RI) was obtained for intratumoral blood flow velocity waveforms by transvaginal Doppler ultrasound and changes in RI (delta RI: differences before and after chemotherapy) were calculated. The tumor volume (TV) was also evaluated, based on the T2-weighted image of magnetic resonance imaging (MRI). The decrease in tumor size [DR-T: (TV before chemotherapy--TV after chemotherapy)/TV before chemotherapy x 100] was determined. RI measurements did not correlate with TV, either before or after chemotherapy. The delta RI varied from 0.007 to 0.615 (mean: 0.207) and DR-T varied from 20.1% to 65.0% (mean: 45.5%). The correlation between delta RI and DR-T [DR-T = 23.5 + 167.2 (delta RI)-165.6 (delta RI)2; R2 = 0.772, p < 0.05] was significant. Therefore, we confirmed the effectiveness of hypertensive intra-arterial chemotherapy for endometrial carcinoma using both transvaginal Doppler ultrasound and MRI.     

Determination of global function and regional mechanics of dynamic cardiomyoplasty using magnetic resonance imaging

This study used tissue tagged magnetic resonance (MR) to assess regional strain and generate pressure-volume (PV) loops in a canine model of cardiomyoplasty (CMP). Three dogs with rapid ventricular pacing induced heart failure underwent dynamic CMP chronic cardiac assistance for 1 year. At the end of the study period, we performed a MR study with the myostimulator "on" and "off" and recording of left ventricular (LV) pressure. We determined the short axis displacement (D) and maximal and minimal principal strains (lambda1 and lambda2) by quantitative two-dimensional regional spatial modulation of magnetization visualization utility image analysis. LV PV loops were generated by combining the LV volume data from the MR images with the LV pressure recorded during imaging. Muscle stimulation produced a leftward shift of the LV PV loops in two of the three dogs, and an increase in LV peak pressure and dp/dt max. In contrast, short axis lambda1 and lambda2 did not change significantly (p = NS). D increased significantly in the anterolateral, posterolateral, and posteroseptal regions (p < 0.05) but did not change for the septal region (p = NS). Flap stimulation augments LV function in the absence of short axis strain change; this suggests that dynamic CMP exerts its main action along the long axis of the heart.     

Correlation between anatomic features and low-field magnetic resonance imaging of the equine metacarpophalangeal joint

OBJECTIVE: To expand our current knowledge and to establish limits of correlation between signal intensities of the magnetic resonance (MR) image and actual macroscopic and microscopic anatomic features of the imaged structures of the equine metacarpophalangeal joint (MCPJ). SAMPLE POPULATION: The right MCPJ was obtained from 4 adult horses that were euthanatized for reasons unrelated to the musculoskeletal system. PROCEDURE: The distal portion of the right forelimbs was collected from 4 equine cadavers. The bones were drilled to provide fixed reference points and examined by MR imaging. After imaging, the joints were sectioned for gross and histologic inspection. The MR images were aligned and correlated with digitized gross and histologic images to identify tissue types. RESULTS: Comparison of the images resulted in identification of different bone types, articular cartilage, and soft tissue structures of the equine MCPJ. CONCLUSION: Results provided relevant information regarding the appearance of the imaged tissues of the equine MCPJ. CLINICAL RELEVANCE: Although MR imaging does not have current clinical applications for equine practitioners, its wide acceptance as the imaging modality used for most human musculoskeletal derangements may aid in developing more realistic applications in equine medicine.     

Primary carcinoid of the duodenum: detection and characterization by magnetic resonance imaging

We report a rare case of a primary small bowel carcinoid in which high-resolution MRI was able to detect a 1-cm primary duodenal neoplasm. This case illustrates that breath-hold contrast-enhanced MRI is capable of evaluating disease of the small bowel.     

Functional and metabolic evaluation of the athlete's heart by magnetic resonance imaging and dobutamine stress magnetic resonance spectroscopy

BACKGROUND: The question of whether training-induced left ventricular hypertrophy in athletes is a physiological rather than a pathophysiological phenomenon remains unresolved. The purpose of the present study was to detect any abnormalities in cardiac function in hypertrophic hearts of elite cyclists and to examine the response of myocardial high-energy phosphate metabolism to high workloads induced by atropine-dobutamine stress. METHODS AND RESULTS: We studied 21 elite cyclists and 12 healthy control subjects. Left ventricular mass, volume, and function were determined by cine MRI. Myocardial high-energy phosphates were examined by 31P magnetic resonance spectroscopy. There were no significant differences between cyclists and control subjects for left ventricular ejection fraction (59+/-5% versus 61+/-4%), left ventricular cardiac index (3.4+/-0.4 versus 3.4+/-0.4 L x min(-1) x m[-2]), peak early filling rate (562+/-93 versus 535+/-81 mL/s), peak atrial filling rate (315+/-93 versus 333+/-65 mL/s), ratio of early and atrial filling volumes (3.0+/-1.0 versus 2.6+/-0.6), mean acceleration gradient of early filling (5.2+/-1.4 versus 5.8+/-1.9 L/s2), mean deceleration gradient of early filling(-3.1 +/- 0.9 versus -3.2 +/- 0.7 L/s2), mean acceleration gradient of atrial filling (3.6+/-1.8 versus 4.5+/-1.7 L/s2), and atrial filling fraction (0.23+/-0.06 versus 0.26+/-0.04, respectively). Cyclists and control subjects showed similar decreases in the ratio of myocardial phosphocreatine to ATP measured with 31P magnetic resonance spectroscopy during atropine-dobutamine stress (1.41+/-0.20 versus 1.41+/-0.18 at rest to 1.21+/-0.20 versus 1.16+/-0.13 during stress, both P=NS). CONCLUSIONS: Left ventricular hypertrophy in cyclists is not associated with significant abnormalities of cardiac function or metabolism as assessed by MRI and spectroscopy. These observations suggest that training-induced left ventricular hypertrophy in cyclists is predominantly a physiological phenomenon.     

Response of MCF7 human breast cancer to tamoxifen: evaluation by the three-time-point, contrast-enhanced magnetic resonance imaging method

Variations in the cellular volume fraction and in the microvascular permeability of MCF7 human breast tumors were used to assess response to tamoxifen. These pathophysiological features were mapped by applying the three-time-point, contrast-enhanced, high resolution magnetic resonance imaging method (H. Degani et al, Nat. Med., 3: 780-782, 1997). Short-term treatment with tamoxifen caused a highly significant increase in the fraction of pixels displaying intermediate contrast agent clearance pattern and a significant increase in the fraction of pixels displaying high rate of contrast agent entrance. These changes resulted from a marked rise in the extracellular volume fraction, indicating increased necrosis, and from an augmentation in the microvascular permeability, predominantly in the vicinity of the high extracellular volume fraction areas, as a result of stress-induced angiogenesis.     

Dialysate pressure isobars in a hollow-fiber dialyzer determined from magnetic resonance imaging and numerical simulation of dialysate flow

A procedure to determine dialysate pressure isobars by comparing the results of magnetic resonance imaging (MRI) and numerical simulation of the dialysate flow was established. The assumption used in the filtration analyses, that the dialysate pressure varies only in the central-axial direction, is supported by the finding that the determined isobars have no steep radial gradient. MRI of the contrast solution permeating the hollow fibers verifies the uniformity of the hollow fiber density in the dialyzer.     

Prediction of tumor control in patients with cervical cancer: analysis of combined volume and dynamic enhancement pattern by MR imaging

BACKGROUND: Hypoxemic developing hearts are susceptible to oxygen-mediated damage that occurs after reintroduction of molecular oxygen. This unintended hypoxemic/reoxygenation injury leads to lipid peroxidation and membrane damage and may contribute to postoperative cardiac dysfunction. Biochemical and functional status are improved by delaying reoxygenation on cardiopulmonary bypass (CPB) until cardioplegic arrest. METHODS: Six immature piglets (3 to 5 kg) without hypoxemia underwent 30 minutes of cardioplegic arrest during 1 hour of CPB. Fourteen others underwent 2 hours of hypoxemia on ventilator before reoxygenation on CPB. Reflecting our clinical routine, 9 were reoxygenated on CPB for 5 minutes followed by 30 minutes of cardioplegic arrest and 25 minutes of reperfusion. The other 5 were put on hypoxemic CPB for 5 minutes, before being reoxygenated during cardioplegic arrest for 30 minutes followed by 25 minutes of reperfusion. RESULTS: Cardioplegic arrest (no hypoxemia group) caused no functional or biochemical changes. In contrast, by preceding hypoxemia with subsequent reoxygenation on CPB (no treatment group) we found 39.5% decrease in antioxidant reserve capacity, 1,212% increase in myocardial conjugated diene production, significant increase in coronary sinus blood conjugated dienes, and an 81% reduction of left ventricular contractility, all of which were statistically significant (p < 0.05) when compared with the no hypoxemia group. Conversely, delaying reoxygenation until cardioplegic arrest (treatment group) resulted in 33.1% improvement in antioxidant reserve capacity, 91.7% less conjugated diene production, lower coronary sinus blood conjugated diene levels, and a 95% improved contractility, all of which were significant (p < 0.05) when compared with the no treatment group. CONCLUSIONS: A reoxygenation injury associated with lipid peroxidation and decreased postbypass contractility occurs in cyanotic immature hearts when reoxygenated on CPB. Delaying reoxygenation until cardioplegic arrest by starting CPB with ambient partial pressure of oxygen results in significantly improved myocardial status.