Cyclin-dependent kinase 6 (CDK6) as a potent regulator of the ovarian primordial-to-primary follicle transition.

Introduction: Ovarian follicle development requires tight coordination between several factors to initiate folliculogenesis to generate a mature and fertile egg. Studies have shown that cell cycle factors might contribute to follicle development, hover specific knowledge on individual CDKs and follicle activation has not been investigated. Among cell cycle regulators, CDK6 is a key player through binding to cyclin D resulting DNA synthesis and genome duplication. Interestingly, the CDK6 gene is differentially expressed in oocytes and granulosa cells from human primordial and primary follicles, which suggest a potential role of CDK6 in the primordial-to-primary transition. In this study, we investigated the potential regulatory role of CDK6 in progression of primordial to primary follicle transition using BSJ-03-123 (BSJ), a CDK6-specific degrader. Methods: In mouse ovarian in vitro culture, BSJ reduced the activation of primordial follicles, and reduced follicle development. As a next step, we examined the egg maturation read-out and found that BSJ-treated follicles matured to competent MII eggs with resumption of first meiosis, comparable with the control group. Results: Noteworthy, it appears that inhibition of CDK6 did increase number of apotoptic cells, articular in the granulosa cells, but had no impact on ROS level of cultured ovaries compared to control group, indicating that the cells were not stressed. Oocyte quality thus appeared safe. Discussion: The results of this study indicate that CDK6 plays a role in the primordial-to-primary transition, suggesting that cell cycle regulation is an essential part of ovarian follicle development.

The α2 Na+/K+-ATPase isoform mediates LPS-induced neuroinflammation.

Na+/K+-ATPase is a transmembrane ion pump that is essential for the maintenance of ion gradients and regulation of multiple cellular functions. Na+/K+-ATPase has been associated with nuclear factor kappa B (NFκB) signalling, a signal associated with lipopolysaccharides (LPSs)-induced immune response in connection with activated Toll-like receptor 4 (TLR4) signalling. However, the contribution of Na+/K+-ATPase to regulating inflammatory responses remains elusive. We report that mice haploinsufficient for the astrocyte-enriched α2Na+/K+-ATPase isoform (α2+/G301R mice) have a reduced proinflammatory response to LPS, accompanied by a reduced hypothermic reaction compared to wild type litter mates. Following intraperitoneal injection of LPS, gene expressions of Tnf-α, Il-1ß, and Il-6 was reduced in the hypothalamus and hippocampus from α2+/G301R mice compared to α2+/+ littermates. The α2+/G301R mice experienced increased expression of the gene encoding an antioxidant enzyme, NRF2, in hippocampal astrocytes. Our findings indicate that α2Na+/K+-ATPase haploinsufficiency negatively modulates LPS-induced immune responses, highlighting a rational pharmacological target for reducing LPS-induced inflammation.

[Update: Clinical imaging of cartilage-part 2 : Aspects helpul in daily clinical practice]. / Update: Klinische Knorpelbildgebung ­ Teil 2 : In der Klinik hilfreiche Aspekte.

BACKGROUND: Imaging-based analysis of articular cartilage and its defects as well as the radiologist have to live up to the more and more specific clinical questions arising from increasing experience with cartilage-dedicated therapies. MATERIALS AND METHODS: Based on the currently available literature and experience from clinical routine, imaging findings relevant for lesion analysis will be summarized and illustrated by specific pathologies. RESULTS: Local aspects and topographic distribution of bone marrow edema pattern (BMEP), careful analysis of the cartilage surface and of the subchondral plate as well as the patient's clinical and biomechanical context are essential for image analysis. Formal grading is helpful to communicate imaging findings, but in itself is not sufficient for a comprehensive analysis. Assessing the stability of a lesion is important for therapy planning. Imaging is helpful to this end, but can be challenging and requires consideration of the arthroscopic and histologic perspective especially when dealing with juvenile osteochondral lesions. DISCUSSION: In order to maximize the therapeutic and prognostic relevance of findings from cartilage imaging, radiologists need to be sensitive to-often very subtle-imaging clues but at the same time we need to be aware of the limitations of our methods.

[Update: clinical imaging of cartilage-part 1 : Technical aspects]. / Update: Klinische Knorpelbildgebung ­ Teil 1 : Technische Aspekte.

BACKGROUND: In order to answer clinical therapy-oriented questions, reliable and consistent depiction of articular cartilage across technical platforms is necessary. MATERIALS AND METHODS: Technical standards and developments in cartilage imaging are summarized based on current literature and experience from clinical daily routine. RESULTS: Clinical questions that need to be answered relate to cross-sectional extent, depth, differentiating cartilaginous from bony components of a lesion and to the lesion's location within the compartment. If present, displaced fragments, concomitant meniscal, ligamentous and/or degenerative lesions should be identified. To date, magnetic resonance imaging (MRI) is the workhorse of cartilage imaging and is largely based on moderately T2-weighted and also proton-density (PD)-weighted fat-suppressed turbo-spin-echo sequences. Direct MR- and CT-arthrography are the gold standard to evaluate thin cartilage layers. Recent advances in coil and MR sequence design, increased availability of 3T-MR scanners and more and more sophisticated acceleration techniques allow for better spatial resolution and more robust image contrast at acceptable scan times. DISCUSSION: As abundant as current developments in clinical routine cartilage imaging may be, the radiologist must carefully select the approach best suited to answering the clinical questions.

Dormancy and activation of human oocytes from primordial and primary follicles: molecular clues to oocyte regulation.

STUDY QUESTION: Do specific transcriptome dynamics in human oocytes from primordial and primary follicles identify novel pathways in oocyte activation? SUMMARY ANSWER: The transcriptomic profiles in oocytes from primordial and primary follicles, respectively, revealed several new canonical pathways as putative mediators of oocyte dormancy and activation. WHAT IS KNOWN ALREADY: Cellular signaling pathways including PI3K/AKT and AKT/mTOR as well as TGF-ß and IGF signaling are known to regulate the primordial-to-primary transition in mammalian follicle development. STUDY DESIGN, SIZE, DURATION: We performed a class comparison study on human oocytes from primordial (n = 436) and primary (n = 182) follicles donated by three women having ovarian tissue cryopreserved before chemotherapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA was extracted from oocytes from primordial and primary follicles isolated by Laser Capture Microdissection, and submitted to the HiSeq Illumina platform. Data mapping, quality control, filtering and expression analysis were performed using Tophat (2.0.4), Cufflinks (2.0.2), BWA (0.6.2) and software R. Modeling of complex biological systems was performed using the IPA® software. Finally, qPCR and immunohistochemistry were employed to explore expression and localization of selected genes and products in human ovarian tissue. MAIN RESULTS AND THE ROLE OF CHANCE: We found 223 and 268 genes down-regulated and up-regulated, respectively, in the oocytes during the human primordial-to-primary follicle transition (P < 0.05 and/or FPKM fold-change >2). IPA® enrichment analysis revealed known pathways ('mTOR Signaling', 'PI3K/AKT Signaling' and 'PTEN Signaling') as well as enriched canonical pathways not previously associated with human ovarian follicle development such as 'ErB Signaling' and 'NGF Signaling' in the down-regulated category and 'Regulation of eIF4 and P70S6K Signaling' and 'HER-2 Signaling in Breast Cancer' in the up-regulated group. Additionally, immunohistochemistry on human ovarian tissue explored the intraovarian localization of VASA, FOXO1 and eIF4E. LARGE SCALE DATA: http://users-birc.au.dk/biopv/published_data/ernst_2017/. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis and no functional studies were performed. The study was based on a limited number of patients and the experimental design could not take into account the natural biological variance in human samples. Therefore, qPCR was used to confirm selected genes alongside immunohistochemical stainings. WIDER IMPLICATIONS OF THE FINDINGS: This study shows, for the first time, a detailed molecular description of global gene transcription activities in oocytes from primordial and primary follicles, respectively. Knowing the global transcription profiles of human oocyte dormancy and activation are important in developing new clinical applications. STUDY FUNDING/COMPETING INTEREST(S): E.H.E. was supported by Health Faculty, Aarhus University and Kong Christian Den Tiendes Fond. K.H. and S.F. were supported by an MRC (UK) project grant MR/M012638/1. K.L.H. was supported by grants from Fonden til Lægevidenskabens Fremme, Kong Christian Den Tiendes Fond. K.L.H. and L.S. were supported by the IDEAS grant from Aarhus University Research Foundation (AUFF). There are no conflicts of interest.

Diagnosis of prostate cancer in patients with persistently elevated PSA and tumor-negative biopsy in ambulatory care: performance of MR imaging in a multi-reader environment.

PURPOSE: False-negative results are obtained in approx. 20 % of prostate cancer (PCa) patients (pts) at initial systematic transrectal biopsy (Bx), in particular when digital rectal examination (DRE) or transrectal ultrasound (TRUS) is negative. The aim of this study was to assess whether MR endorectal imaging of the prostate in a multi-reader ambulatory care setting may assist in patient selection for re-biopsy. MATERIALS AND METHODS: 115 consecutive pts with persistent PSA elevation, negative Bx, DRE and TRUS were examined using T2w axial and coronal and T1w axial sequences for tumor diagnosis. MR images were prospectively read as tumor-suspicious or tumor-negative by the MR radiologist on duty. Additionally, a retrospective readout of a prostate MR expert and an abdominal imaging fellowship-trained radiologist was performed to evaluate the effect of the reader's experience on tumor detection. Imaging findings were compared to the results of the repeat Bx (61 pts) or the clinical course of at least two years. RESULTS: For the prospective reading, the sensitivity of MRI was 83 %, the specificity was 69 %, the PPV was 33 % and the NPV was 96 %. ROC analysis revealed a significantly better performance of the prostate MR imaging expert compared to the abdominal imaging radiologist (area under ROC 0.88 vs. 0.66, p < 0.001). Based on the prospective reading, a pre-test probability for PCa of 17.4 % as in our study can be reduced to 5 % when obtaining a tumor-negative result in MRI. CONCLUSION: MR imaging in a multi-reader ambulatory care setting assists in patient selection for re-biopsy. Reducing the post-test probability for PCa to 5 % allows for further follow-up instead of re-biopsy in MR tumor-negative patients. Specific training and experience improve tumor detection in prostate MR imaging.

Combined MRI and MRS in prostate cancer: improvement of spectral quality by susceptibility matching.

PURPOSE: Local magnetic field inhomogeneity caused by susceptibility artifacts due to air in the endorectal coil substantially degrades the quality of 3D MR spectroscopic imaging (3D-MRSI). Perflubron (PFB) has magnetic susceptibility similar to that of human tissue. We prospectively assessed the effect of susceptibility matching using PFB on in vivo prostate (1)H-3D-MRSI. MATERIALS AND METHODS: Ninety-one consecutive patients referred for 3D-MRSI were examined using air and PFB as the filling agent for endorectal coils at 1.5T with an identically placed PRESS box and sat bands. Solely auto-shim without additional manual shimming was used. The full width at half maximum (FWHM) of the water peak was statistically compared with a paired t-test. The spectral quality was visually evaluated for the definition of metabolite peaks and for the citrate peak split (duplet). The MR image quality was rated on a five-point scale. RESULTS: FWHM was significantly less (p < 0.001) using PFB (mean 9.0 +/- 3.3, range 3 - 20) than air (mean 14.9 +/- 4.2, range 6 - 26) in 85/91 patients (93%). The spectral quality markedly improved using PFB and frequently the duplet of the citrate peak was able to be identified. Image quality ratings were similar (mean rating PFB 4.2, air 4.3 points). Omitting manual shimming led to a time savings of 4 min. per study. CONCLUSION: 3D-MRSI using PFB for susceptibility matching benefits from significantly better local field homogeneity, thus providing improved spectra quality. Combined with a substantial time savings in data acquisition, this may increase the clinical utilization of 3D-MRSI in patients with prostate cancer.

Directional mRNA transport in eukaryotes: lessons from yeast.

In eukaryotes, developmental processes and cell differentiation, as well as basic cellular functions require the propagation of information in an asymmetric manner. Localization of mRNA is a key mechanism to establish asymmetric cell fate. The first part of this review provides an overview of our current knowledge of motor protein-dependent mRNA transport in eukaryotes. The second part provides a more detailed description of the most comprehensively studied mRNA translocation complex to date: the ASH1 messenger ribonucleoprotein particle (mRNP) from Saccharomyces cerevisiae. During budding of yeast, the ASH1 mRNP transports cell fate determinants exclusively into the daughter cell. The core factors of the ASH1 mRNP have been identified, their interactions have been studied in detail, and the three-dimensional structure of its mRNA-binding protein, She2p, has been determined. Because no other mRNP has been studied in such detail, the ASH1 mRNP could serve as a model for asymmetric segregation of cell fate determinants in higher eukaryotes.

[Meniscus and ligament injuries]. / Meniskus- und Bandläsionen.

The knee is one of the major weight-bearing joints and is relatively exposed to trauma. Capsuloligamentous structures are essential to provide joint stability and -- in turn -- persistent instability bears a risk for osteoarthritis that needs timely and comprehensive diagnosis. Using MRI it may be beneficial to routinely apply (T)SE sequences in all three major planes as a basic protocol and to add additional sequences according to the clinical information available and imaging findings in the basic protocol. Especially fat-suppressed sequences (STIR, T2w/PDw FS TSE) are very useful because they sensitively depict bone marrow edema pattern (BMEP)-like changes. This finding often alerts the reader to -- sometimes only discrete -- underlying pathologies and may -- if found in typical locations -- give information about the mechanism of injury and thus lead the radiologist to look for specific concomitant capsuloligamentous, cartilage, and/or meniscal injury. BMEP is quite prominent in contusion injury, whereas often it is but discrete in avulsion lesions. There is extensive literature about the signs, possible pitfalls, and the accuracy of MRI for the diagnosis of specific pathologies such as meniscal tears or cruciate or collateral ligament ruptures. However, combined injuries of more than one structure are frequent and affect the therapeutic approach. Thus, the primary goal of the radiologist is to go beyond the description of any isolated lesion and to give a comprehensive description of (or to reliably exclude) any injury to other structures. A necessary prerequisite to accomplish this is a thorough knowledge of the -- in some locations -- complex anatomic relationships, pitfalls, and locations where lesions typically occur and where they may be overlooked.

[MR imaging of prostate cancer]. / MR-Tomographie des Prostatakarzinoms.

PURPOSE: Accurate diagnosis and staging of prostate cancer (PC) is developing into an important health care issue in light of the high incidence of PC and the improvements in stage-adapted therapy. The purpose of this paper is to provide an overview on the current role of MR imaging and MR spectroscopy in the diagnosis and staging of PC. MATERIAL AND METHODS: Pertinent literature was searched and evaluated to collect information on current clinical indications, study techniques, diagnostic value, and limitations of magnetic resonance imaging and spectroscopy. RESULTS: Major indications for MR imaging of patients with suspected PC are to define tumor location before biopsy when clinical or TRUS findings are inconclusive, and to provide accurate staging of histologically proven PC to ascertain effective therapy. Current MR imaging techniques for the evaluation of PC include multiplanar high-resolution T2-weighted FSE and T1-weighted SE sequences using combined endorectal and phased-array coils. Using these techniques, the reported accuracy of MR imaging for the diagnosis of extracapsular tumor extension ranges between 82 and 88% with sensitivities between 80 and 95%, and specificities between 82 and 93%. Typical MR findings of PC in different stages of disease, as well as diagnostic problems, such as chronic prostatitis, biopsy-related hemorrhage and therapy-related changes of prostatic tissue are discussed. In addition, the current perspectives and limitations of MR spectroscopy in PC are summarized. CONCLUSIONS: Current MR imaging techniques provide important diagnostic information in the pretherapeutic workup of PC including a high staging accuracy, and is superior to TRUS.

Contrast-enhanced MR angiography in patients after kidney transplantation.

The aim of this study was to investigate the value of a contrast-enhanced 3D MR angiography in detecting postoperative vascular complications after kidney transplantation in comparison with digital subtraction angiography (DSA). Forty-one patients who underwent a kidney transplantation were examined with MR angiography and DSA. Contrast-enhanced MR angiography was performed as a dynamic measurement with one precontrast and three postcontrast measurements. Maximum intensity projection reconstructions were performed for all postcontrast data sets after DSA. The results were evaluated by two independent observers who were unaware of the DSA results. Twenty-three hemodynamically significant arterial stenoses were identified with DSA in the iliac arteries ( n=7), the renal allograft arteries ( n=12), and in their first branches ( n=4). For a patient-based analysis the sensitivity and specificity, respectively, for observer 1 were 100 and 97%, and for observer 2, 100 and 93%. Respective data were 100 and 100% after a consensus evaluation by two observers. Complications involving the renal veins were detected in 2 cases and perfusion defects of the kidney parenchyma were detected in 4 cases. Contrast-enhanced MR angiography is a reliable method in identifying postoperative arterial stenoses after kidney transplantation. In addition, dynamic MR angiography can be helpful in detecting venous complications and perfusion defects in kidney allografts.

[Benign bone-forming tumors]. / Gutartige knochenbildende Tumoren.

Benign bone-forming tumors include osteomas, enostomas, osteoid osteomas, and osteoblastomas. These lesions are often characterized by typical imaging findings on radiographs, CT and MR imaging studies. Radiologic findings and additional clinical information allow for a specific diagnosis in most cases. This review article emphasizes the radiological patterns of benign bone-forming tumors as well as their epidemiological, clinical, and pathological characteristics. In addition, minimally invasive interventional procedures for the therapy of osteoid osteoma are reviewed.

Carpal tunnel syndrome: assessment by turbo spin echo, spin echo, and magnetization transfer imaging applied in a low-field MR system.

PURPOSE: The purpose of this work was to evaluate patients with carpal tunnel syndrome (CTS) using a low-field extremity MR system (E-MRI: 0.2 T). METHOD: Twenty-two patients with typical findings of CTS and 30 control persons were imaged on an E-MRI. Axial T2-weighted turbo SE (TSE), T1-weighted SE sequences, and 2D GRE magnetization transfer (MTC) sequences were compared. SE and MTC sequences were obtained before and after contrast agent administration (0.1 mmol/kg body wt of Gd-DTPA). Two readers evaluated typical MR findings of CTS independently. RESULTS: Patients with CTS demonstrated palmar bowing of the flexor retinaculum significantly more often. The normal or edematous median nerve was best identified on TSE and MTC scans (kappa = 0.59 and 0.8). The MTC sequences showed perineural enhancement significantly better than respective T1-weighted SE sequences but were rated second in comparison with T2-weighted TSE scans. CONCLUSION: At low-field strength, median nerve edema is best depicted on T2-weighted TSE sequences, whereas MTC sequences are most sensitive to perineural contrast enhancement.

Perioperative prediction by MRI of prostate volume six to twelve months after laser-induced thermotherapy of benign prostatic hyperplasia.

The purpose of this study was to predict prostate volume outcome 6-12 months after interstitial, laser-induced thermotherapy (LITT) for benign prostatic hyperplasia (BPH) on the basis of prostate magnetic resonance (MR) images obtained within 48 hours before and after LITT. Twenty patients (age, 64.2 +/- 7.4 years) with symptomatic BPH had LITT of the transitional zone of the prostate. MRI was performed within 48 hours before and after LITT, and 6-12 months after LITT (late follow-up). MRI included axial and sagittal T2-weighted fast spin-echo (FSE) images and contrast-enhanced, axial T1-weighted images. Volumes of different prostatic compartments (total prostate, transitional zone, peripheral zone, LITT lesions) were measured by planimetry. Subtraction of LITT lesion volume less than 48 hours after LITT from total and transitional zone volume before LITT, respectively, predicted respective prostatic volumes at late follow-up. Pearson correlations of predicted and measured total prostate and transitional zone volumes were 0.972 and 0.975, respectively. Total prostate volume at late follow-up was accurately predicted (difference, -0.5 +/- 5.7 cc; P = 0.6981, two-tailed paired t-test). Transitional zone volume was underestimated (difference, -3.1 +/- 4.7 cc; P = 0.0075). Peripheral zone volume was overestimated (difference, 2.6 +/- 3.5 cc; P = 0.0034). Perioperative MRI allows accurate prediction of prostate volume 6-12 months after LITT for BPH. Underestimation of transitional zone volume may be due to ongoing growth of BPH. LITT appears to affect peripheral zone tissue outside the target region. J. Magn. Reson. Imaging 2001;13:64-68.

Mechanism of membrane insertion of a multimeric beta-barrel protein: perfringolysin O creates a pore using ordered and coupled conformational changes.

Perfringolysin O, a bacterial cytolytic toxin, forms unusually large pores in cholesterol-containing membranes by the spontaneous insertion of two of its four domains into the bilayer. By monitoring the kinetics of domain-specific conformational changes and pore formation using fluorescence spectroscopy, the temporal sequence of domain-membrane interactions has been established. One membrane-exposed domain does not penetrate deeply into the bilayer and is not part of the actual pore, but is responsible for membrane recognition. This domain must bind to the membrane before insertion of the other domain into the bilayer is initiated. The two domains are conformationally coupled, even though they are spatially separated. Thus, cytolytic pore formation is accomplished by a novel mechanism of ordered conformational changes and interdomain communication.

[The diagnosis of metastases in the bone marrow by MRT]. / Diagnostik der Metastasierung im Knochenmark mittels MRT.

MRI plays an important role in the diagnostic workup of skeletal metastases. In principle two different applications of MRI can be distinguished: apart from the well known indications of clarifying uncertain lesions seen with other imaging modalities or demonstrating known osseous lesions with high resolution imaging for therapeutic planing, MRI can also be used as a primary screening modality for skeletal metastases. Besides the higher lesion detection rate the major advantage of MRI compared to bone scintigraphy lies in the demonstration of morphology which on the one hand exactly shows the extension of tumorous lesions and on the other hand clearly distinguishes between malign and benign processes. As unclear findings on bone scintigraphy often require additional imaging studies, especially in patients with clinical findings or lab results suggestive for metastatic disease, we think that whole-body-skeletal-MRI is not only an accurate but also a cost effective diagnostic modality in the detection and screening for skeletal metastases, if the indication for the examination is closely related to clinical findings and the therapeutic relevance of the imaging results.

Dynamic contrast-enhanced MR angiography from the distal aorta to the ankle joint with a step-by-step technique.

OBJECTIVE: The aim of this study was to visualize the arteries from the distal aorta to the ankle joint and to determine the accuracy of MR angiography for detecting stenoses and occlusions. SUBJECTS AND METHODS: Twenty-four patients with peripheral arterial occlusive disease underwent digital subtraction angiography and were examined on a 1.5-T MR scanner. The transit time for contrast material was determined with a test bolus injection. A T1-weighted three-dimensional gradient-echo sequence with short TR and TE was used for a dynamic measurement at the level of the iliac arteries, the upper leg, and the lower leg arteries. For each level a single dose of gadolinium was injected into an antecubital vein with an MR power injector. Maximal-intensity-projection reconstructions were calculated after subtraction of the first measurement at each level. Two experienced MR radiologists who were unaware of the digital subtraction angiography results interactively evaluated both the MIP reconstructions and the single slices on a workstation, first independently and then in a consensus interpretation. RESULTS: With digital subtraction angiography, 80 hemodynamically significant stenoses and 39 occlusions were detected. For the stenoses and occlusions, a sensitivity of 100% was found for MR angiography. The specificity for the assessment of stenoses and occlusions was 98% and 94%, respectively, for the iliac arteries; 98% and 94%, respectively, for the upper leg arteries; and 94% and 95%, respectively, for the lower leg arteries. Most false-positive findings of occlusion were due to metal stents present in the iliac (n = 3) and upper leg (n = 4) arteries. CONCLUSION: The MR imaging technique that we used revealed the arteries from the distal aorta to the ankle and proved to be reliable at showing arterial stenoses and occlusions.

Effects of three different doses of a bolus injection of gadodiamide: assessment of regional cerebral blood volume maps in a blinded reader study.

BACKGROUND AND PURPOSE: Reconstruction of first-pass bolus information to derive regional cerebral blood volume (rCBV) maps is commonly performed in many centers; however, various protocols with different doses of paramagnetic contrast injections have been reported. We evaluated the dose dependency of rCBV maps in a brain tumor population by using three different doses of gadodiamide injection to evaluate their diagnostic accuracy in blinded reader sessions. METHODS: Eighty-three patients with intraaxial brain tumors (72 gliomas) were studied at three centers and randomized to receive a bolus injection of 0.1, 0.2, or 0.3 mmol/kg per body weight of gadodiamide. rCBV maps were generated from T2*-weighted gradient-echo echoplanar sequences at 1.5 T. Data processing was performed according to the indicator dilution theory. RESULTS: The mean contrast-to-noise ratio (CNR) was significantly different between gadodiamide doses of 0.1 and 0.2 mmol/kg (CNR = 8.7 and 15.7) and between 0.1 and 0.3 mmol/kg (CNR = 17.7). No significant difference was found between doses of 0.2 and 0.3 mmol/kg. Sensitivity for the differentiation of benign and malignant brain tumors was 80%, 95%, and 91%, and specificity was 45%, 54%, and 43% by blinded readings at 0.1, 0.2, and 0.3 mmol/ kg, respectively, as compared with histologic findings. Nonblinded readings had a sensitivity of 83%, 100%, and 90% and a specificity of 82%, 100%, and 73% at 0.1, 0.2, and 0.3 mmol/kg, respectively. CONCLUSION: A dose of 0.2 mmol/kg of gadodiamide is recommended for reconstruction of rCBV maps if data are acquired with the T2*-weighted protocol described.