H. Hawighorst

Evaluation of angiogenesis and perfusion of bone marrow lesions: Role of semiquantitative and quantitative dynamic MRI

Magnetic resonance imaging (MRI) is a noninvasive technique that complements computed tomography (CT), conventional X‐ray, and bone marrow biopsies by sampling a large volume of musculoskeletal bone and providing information that aids the diagnosis, staging, and follow‐up of various lesions. Although less sensitive to the mineral components of bones, the MRI appearance of physiologic bone marrow is mainly a reflection of the relative amounts of red marrow, yellow marrow, and trabecular bone. Therefore, use of T1‐and T2‐weighted MR sequences with or without fat suppression currently remains the most common approach to musculoskeletal bone lesion imaging. An additional imaging strategy to characterize various bone lesions is the application of contrast‐enhanced dynamic MRI. This article examines semiquantitative and quantitative dynamic imaging, evaluation, and postprocessing techniques in various benign and malignant musculoskeletal lesions. Practical guidelines for performing a dynamic contrast‐enhanced MR examination are proposed. J. Magn. Reson. Imaging 1999; 10:286–294.

Transient enlargement of contrast uptake on MRI after linear accelerator (linac) stereotactic radiosurgery for brain metastases

PURPOSE/OBJECTIVE With the increasing number of patients successfully treated with stereotactic radiosurgery for brain metastases, decision making after therapy based on follow-up imaging findings becomes more and more important. Magnetic resonance imaging (MRI) is the most sensitive means for follow-up studies. The objective of this study was to investigate the treatment outcome of our radiosurgery program and to describe the response of brain metastases to contrast-enhanced MRI after linear accelerator (linac) stereotactic radiosurgery and identify factors to distinguish among local control and local failure. METHODS AND MATERIALS Using serial MRI, we followed the course of 87 brain metastases in 48 consecutive patients treated between September 1996 and November 1997 with linac-based radiosurgery with 15-MV photons. Treatment planning was performed on an MR data cube. For spherical metastases, radiosurgery was delivered using a 9 noncoplanar arc technique with circular-shaped collimators. For irregularly shaped targets, radiosurgery was delivered using a manually driven multi-leaf collimator with a leaf width of 1.5 mm projected to the isocenter. Median radiosurgery dose was 20 Gy prescribed to the 80% isodose. Together with whole brain radiotherapy (20 x 2 Gy, 5/w), a median radiosurgical dose of 15 Gy was delivered. Median follow-up was 8 (range 2--36) months. Factors influencing local control and survival rates were analyzed with respect to MRI response, and Kaplan-Meier curves were calculated. RESULTS Actuarial local tumor control was 91% at one and two years. Patient survival at one and two years was 30% and 18%. Median survival was 9 months. During follow-up in 70 (81%) of the 87 treated metastases, the contrast-enhancing volumes on T1W images were stable or disappeared partly or completely. A transient enlargement of contrast-enhancing volumes was observed in 11 (12%) of the 87 lesions treated, while a progressive enlargement due to local treatment failure was observed in 6 (7%) of the 87 treated metastases. Younger age, early contrast onset after radiosurgery, and previous chemotherapy were associated with this transient enlargement of contrast-enhancing lesion volume. CONCLUSIONS Linac-based radiosurgery is an effective, noninvasive, and safe treatment option for patients with brain metastases. A marked enlargement of the contrast-enhancing volume on T(1)-weighted MR images after radiosurgery is a sensitive predictor for, but not equivalent with, local failure. In as many as two-thirds of the cases with contrast enlargement in MRI follow-up, the contrast enlargement is transient with no need for further treatment. While some MRI findings are more likely if transient enlargement is present, a clear decision cannot be made based on MRI, and ultimately the clinical status dictates further action.

Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging

The aim of our study was to investigate the quantitative microcirculation parameters amplitude A (hypothetical intravascular volume) and exchange rate constant k21 (hypothetical vascular permeability) by contrast‐enhanced dynamic magnetic resonance imaging (dMRI) as markers of angiogenesis in multiple myeloma (MM). Therefore lumbar spine and spina iliaca superior posterior of 16 normal controls and 41 patients with active MM were assessed using a dMRI protocol with a pump controlled bolus infusion of Gadolinium‐DTPA. Pharmacokinetic parameters, amplitude A and exchange rate constant k21 were calculated according to a 2‐compartment model. Color‐coded parameter images were generated from pharmacokinetic data analysis and superimposed onto the conventional MR images. Amplitude A and k21 parameters were significantly increased in patients with MM compared with controls (p = 0.001; median Actr, 0.2 [range, 0.09–0.4]; median AMM, 0.93 [range, 0.2–2.2]; median k21ctr, 0.09 min−1 [range, 0.03–0.9]; median k21MM, 4.58 [range, 0.22–23.8]). Within the group of MM patients the pattern of color‐coded parameter images were found to be either of “diffuse” (n = 13, 31%) or “focal” (n = 28, 69%) type of distribution of microcirculation. Comparison of amplitude A in patients with “focal” vs. “diffuse” pattern of the pharmacokinetic maps revealed a significant increase in the median of amplitude A in the “focal” group. Amplitude A values allowed a classification of patients according to severe osteolytic bone involvement (p = 0.023) with the best cutoff value of 0.7 for amplitude A. Downmodulation of amplitude A was observed in a MM patient treated with standard VAD chemotherapy. Our data demonstrate that dMRI is a novel imaging technique for the detection and monitoring of MM bone lesions. It provides independent evidence for angiogenesis in MM.

Staging of invasive cervical carcinoma and of pelvic lymph nodes by high resolution MRI with a phased-array coil in comparison with pathological findings

PURPOSE Our goal was to stage invasive cervical carcinoma (pT1b-pT4a) and pelvic lymph nodes by high resolution MRI with a circularly polarized (cp) phased-array coil in correlation with the whole-mount specimen and the histopathological findings. METHOD Thirty-three patients (20-68 years old; mean age 55 years) with biopsy-proven primary cancer of the cervix were prospectively examined on a 1.5 T scanner by using a cp body phased-array coil. The MR protocol consisted of high resolution T2-weighted turbo-SE (TSE) and pre- and postcontrast T1-weighted SE (SE) sequences. Slice thickness was 5-7 mm with a pixel size of 0.3-0.4 mm2. All MRI findings were matched to the whole-mount specimens and the histopathological findings. RESULTS Pathological stages evaluated were pT1b (n = 5), pT2b (n = 16), and pT4a (n = 12). The overall accuracy rates for tumor staging were 79% for high resolution T2-weighted TSE and 76% for postcontrast T1-weighted SE images. The accuracy for high resolution T2-weighted TSE images in determining parametrial infiltration, pelvic side wall, and bladder and rectal wall infiltration was 84, 87, and 87%, respectively. In prospective analysis of the 1.0 cm criterion for diagnosis of a positive pelvic lymph node, MRI had a 72% accuracy, a 68% sensitivity, and a 78% specificity. CONCLUSION High resolution MRI with a cp body phased-array coil provides excellent and robust high resolution images in patients with invasive cervical carcinoma. However, accuracy, specificity, and sensitivity for staging invasive cervical carcinoma and pelvic lymph nodes with correlation to whole-mount specimens and histopathological findings did not improve compared with the results in the literature using a body coil with thicker slices and a lower spatial resolution.

Intracranial meningeomas: Time- and dose-dependent effects of irradiation on tumor microcirculation monitored by dynamic MR imaging

The purpose of this study was the characterization of the time- and dose-dependent effects of irradiation on tumor microcirculation by means of dynamic MR imaging and correlation of the estimated data with tumor response in patients with meningeomas. Dynamic MR imaging studies were performed in 20 patients with intracranial meningeomas prior to (n = 20) and at 6 (n = 17), 18 (n = 17), and 50 wk (n = 14) after the end of radiotherapy. In seven of these patients, dynamic measurements were also performed during fractionated radiotherapy after approximate 20 Gy and 54 Gy. During and after short-time infusion of gadopentetate dimeglumine, the kinetics of lesion response was resolved using a strongly T1-weighted saturation recovery TurboFLASH (SRTF) sequence. The signal-time courses of the suspected lesions were analyzed using a pharmacokinetic two-compartment model. The calculated parameters amplitude A (reflecting gadopentetate dimeglumine accumulation in the extracellular space) and exchange rate constant k21 (depending on vascular permeability and blood flow) were displayed as color-coded images and analyzed as a function of time of therapy and radiation dose. All meningeomas showed a high exchange rate constant k21 (median, 5.7 min-1; range, 1.9-23.0 min-1) and a high amplitude A (median, 1.5 arbitrary units; range, 1.1-2.7) prior to X-ray treatment. During radiotherapy we found a dose related significant (p < .01) increase of k21 accompanied by an increase of the amplitude A as compared to the pretreatment values. Analysis of tumor volume 6, 18, and 50 wk after X-ray treatment revealed two different groups. In the responder group (n = 13) the median of the tumor volume decreased from 10.0 to 7.5 cm3. For this group, we found a significant drop (p < .01) of the median of the amplitude A and a decrease of the exchange rate constant k21. In the nonresponder group (n = 4) the median of the tumor volume increased after radiation from 3.5 to 4.5 cm3. The pharmacokinetic analysis revealed a decrease of the amplitude A-and an increase of the exchange rate constant k21. The response of meningeomas to radiotherapy is influenced by the effect of X-rays on tumor microcirculation. This effect on tumor microcirculation can be derived by analysis of pharmacokinetic maps obtained from dynamic MR images. Furthermore, these pharmacokinetic maps can possibly be used to differentiate groups of patients who respond or do not respond to radiotherapy and, thus, could benefit from another treatment modality.

Cerebral arteriovenous malformations: Improved nidus demarcation by means of dynamic tagging MR-angiography

Our purpose was to further improve the target volume definition for radiosurgical treatment of cerebral arteriovenous malformations (AVMs) by means of dynamic MRA (dMRA) using a blood bolus tagging sequence. We therefore compare this technique with 3D-TOF-MRA and transfemoral high resolution angiography in plain film technique. Twenty patients with angiographically proven cerebral AVMs were investigated by dMRA, TOF-MRA, and conventional angiography during the MR-assisted radiosurgical planning protocol. The patients head was fixed in an MR-compatible stereotactic device. The different angiography techniques were evaluated by consensus of two radiologists. AVMs were characterized by the number and origin of feeding arteries, the maximum diameter of the AVM nidus, and the venous drainage pattern. Dynamic MRA was able to demonstrate the complete AVM characteristics and hemodynamics in 12 out of 20 patients. In three patients with an AVM nidus smaller than 1 cm in diameter the technique could not reliably depict the malformation. Technical problems due to steel screws and pins in the initially used stereotactic frame occurred in five patients. Due to reduced vessel overlap and the lack of disturbances caused by formations with short T1 time, dMRA was superior to TOF-MRA in the detection and the exact localization of the AVM nidus in four patients. We conclude that dMRA is able to demonstrate reliably AVM characteristics and hemodynamics in AVMs with a nidus larger than 1 cm in diameter. Because of the improved demarcation of the AVM nidus, this technique may be a valuable adjunct to radiosurgery planning of cerebral AVMs.

Fluid-attenuated inversion-recovery MR imaging of gliomatosis cerebri

Abstract Magnetic resonance imaging has been shown to be the most sensitive imaging modality in the assessment of gliomatosis cerebri. Recent studies have shown that fluid-attenuated inversion-recovery (FLAIR) is a valuable MR sequence in the delineation of cerebral pathologies including intra-axial tumors. However, no data are available about the role of this novel technique in the assessment of gliomatosis lesions. The purpose of this study was therefore to evaluate the diagnostic potential of FLAIR MR imaging in patients with suspected gliomatosis cerebri. Seven patients suspected of having lesions of gliomatosis cerebri were examined by T1-weighted spin echo (SE), T2-weighted fast spin echo (FSE), and FLAIR MR imaging with identical slice parameters. T1 and FLAIR were repeated after contrast media administration. Delineation and extent of gliomatosis were the primary parameters of the image analysis. The FLAIR imaging clearly delineated the extent of gliomatosis lesions in all patients. Due to the suppression of cerebrospinal fluid, the delineation was superior to conventional T2-weighted FSE images. Especially the detection and delineation of cortical spread and the infiltration of the corpus callosum was best seen on FLAIR images. The FLAIR MR imaging is a valuable diagnostic modality in the assessment of patients with gliomatosis cerebri. Due to its better delineation of tumor spread, it was found to be the imaging method of choice and should therefore be integrated into the MR imaging protocol of these patients.

Comprehensive MR evaluation of renovascular disease in five breath holds.

To detect a renal artery stenosis and assess its hemodynamic and functional significance in five breath holds. In a single MR exam, T1 weighted FLASH and T2 weighted fast spin echo techniques are used to assess renal morphology, multiphase 3D gadolinium (Gd) MRA to evaluate the renal arteries, and a segmented EPI cine phase‐contrast technique to measure renal artery blood flow. A standardized image analysis is performed to assess kidney size, corticomedullar differentiation (CMD), parenchymal enhancement, the degree of renal artery stenosis, abnormalities in blood flow pattern, and any associated abdominal vascular disease. Multiphase 3D‐Gd‐MRA accurately assesses atherosclerotic renal artery disease particularly in the presence of an associated aortic aneurysm. Delayed parenchymal enhancement, loss of CMD, and decrease in kidney size can be detected. In combination with decreased systolic velocity components, the diagnosis of a hemodynamically and functionally significant stenosis can be made. High‐resolution single‐phase 3D‐Gd‐MRA is preferable for evaluation of fibromuscular dysplasia or hypoplastic vessels. The combination of different breath hold techniques in a single, standardized MR exam allows to detect the hemodynamic and functional significance of a renal artery stenosis. J. Magn. Reson. Imaging 1999;10:347–356.

Abdominal aortic aneurysm. Detection of multilevel vascular pathology by time-resolved multiphase 3D gadolinium MR angiography: initial report.

OBJECTIVE To evaluate multiphasic 3D gadolinium-enhanced magnetic resonance angiography (3D-Gd-MRA) for detection of vascular pathology at multiple levels of the aorta and iliac arteries. METHODS In 18 patients with abdominal aortic aneurysm (n = 13), dissection (n = 3), or both (n = 2), multiphase 3D-Gd-MRA was performed acquiring five consecutive (6.8 seconds) 3D data sets in a single breath-hold. In each of the five time-resolved phases, vessel visibility of the abdominal aortic branches and iliac arteries was assessed. The extent of vessel involvement by the aneurysm or dissection seen on multiphase 3D-Gd-MRA was compared with standard imaging and surgical findings. Digital subtraction angiography was available for comparison in 4 cases, CT angiography in 10 cases. RESULTS Due to the delayed filling of the aortic aneurysm, the proximal aortic branches and the aneurysm neck demonstrated an inversely related enhancement compared with the distal abdominal and iliac vessels (P < 0.001). Review of all five phases of multiphase 3D-Gd-MRA allowed optimal visualization of each vessel segment without any artifacts due to parenchymal or venous overlay. In dissections, review of three phases was required (P < 0.001) for diagnostic evaluation of the true and false lumens. Substantially more vessel involvement was detected on multiphase 3D-Gd-MRA; this was surgically confirmed in 10 of 11 cases and affected therapy management in 11 of 18 cases. CONCLUSIONS Multiphase 3D-Gd-MRA is a convenient, robust, and safe technique for presurgical anatomic mapping of complex aortic aneurysms and dissections.

Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival

Since detailed knowledge regarding the pathophysiological properties—which in turn are responsible for differences in contrast enhancement—remain fairly undetermined, it was the aim of this study (i) to examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis (microvessel density [MVD]; vascular endothelial growth factor [VEGF]) and (ii) to determine the ultimate value of a histomorphological and a dynamic MRI approach by correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, exchange rate constantk21) and standard parameters (maximum signal intensity (SI)-increase, [SI-I] over baseline and steepest SI-upslope, per second [SI-U/s]) were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with similar sized and positioned regions-of-interest (ROIs) on the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found betweenMVD and amplitudeA (P<0.01) andSI-I (P<0.05). No significant relationships were observed between theVEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based onk21and SI-U/s showed that tumors with highk21 andSI-U/s values had a significantly (P<0.05, 0.001, respectively) worse disease outcome than tumors with lowk21 andSI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD, VEGF) had any significant power to predict patient survival. It is concluded that (1) the pathophysiological basis for differences in dynamic MRI isMVD but not VEGF-expression; (2) a functional, dynamic MRI approach (both standard and a pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis; and [3] compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assessMVD or patient survival.