Bertine L. Stehouwer

Magnetic resonance imaging in breast cancer: A literature review and future perspectives

Early detection and diagnosis of breast cancer are essential for successful treatment. Currently mammography and ultrasound are the basic imaging techniques for the detection and localization of breast tumors. The low sensitivity and specificity of these imaging tools resulted in a demand for new imaging modalities and breast magnetic resonance imaging (MRI) has become increasingly important in the detection and delineation of breast cancer in daily practice. However, the clinical benefits of the use of pre-operative MRI in women with newly diagnosed breast cancer is still a matter of debate. The main additional diagnostic value of MRI relies on specific situations such as detecting multifocal, multicentric or contralateral disease unrecognized on conventional assessment (particularly in patients diagnosed with invasive lobular carcinoma), assessing the response to neoadjuvant chemotherapy, detection of cancer in dense breast tissue, recognition of an occult primary breast cancer in patients presenting with cancer metastasis in axillary lymph nodes, among others. Nevertheless, the development of new MRI technologies such as diffusion-weighted imaging, proton spectroscopy and higher field strength 7.0 T imaging offer a new perspective in providing additional information in breast abnormalities. We conducted an expert literature review on the value of breast MRI in diagnosing and staging breast cancer, as well as the future potentials of new MRI technologies.

Ultra high spatial and temporal resolution breast imaging at 7T

There is a need to obtain higher specificity in the detection of breast lesions using MRI. To address this need, Dynamic Contrast‐Enhanced (DCE) MRI has been combined with other structural and functional MRI techniques. Unfortunately, owing to time constraints structural images at ultra‐high spatial resolution can generally not be obtained during contrast uptake, whereas the relatively low spatial resolution of functional imaging (e.g. diffusion and perfusion) limits the detection of small lesions. To be able to increase spatial as well as temporal resolution simultaneously, the sensitivity of MR detection needs to increase as well as the ability to effectively accelerate the acquisition. The required gain in signal‐to‐noise ratio (SNR) can be obtained at 7T, whereas acceleration can be obtained with high‐density receiver coil arrays. In this case, morphological imaging can be merged with DCE‐MRI, and other functional techniques can be obtained at higher spatial resolution, and with less distortion [e.g. Diffusion Weighted Imaging (DWI)]. To test the feasibility of this concept, we developed a unilateral breast coil for 7T. It comprises a volume optimized dual‐channel transmit coil combined with a 30‐channel receive array coil. The high density of small coil elements enabled efficient acceleration in any direction to acquire ultra high spatial resolution MRI of close to 0.6 mm isotropic detail within a temporal resolution of 69 s, high spatial resolution MRI of 1.5 mm isotropic within an ultra high temporal resolution of 6.7 s and low distortion DWI at 7T, all validated in phantoms, healthy volunteers and a patient with a lesion in the right breast classified as Breast Imaging Reporting and Data System (BI‐RADS) IV. Copyright

7 T versus 3 T contrast-enhanced breast Magnetic Resonance Imaging of invasive ductulolobular carcinoma: First clinical experience

PURPOSE Here we describe our first experience with contrast-enhanced (CE) MRI of breast cancer at 7 tesla (T), compared to 3T and histopathology. MATERIALS AND METHODS A 52 year old female patient with a mammographically suspicious breast mass (BI-RADS V) underwent 7 T CE-MRI. Results were described according to the BI-RADS-MRI criteria and compared to 3T and histopathology. RESULTS After contrast administration, a homogeneously enhancing, irregular spiculated mass was depicted at both 3T and 7 T; sizes were identical. The most malignant kinetic curve was characterized by a rapid initial rise followed by a wash-out pattern in the delayed phase, i.e. a type 3 curve, at both field strengths. Even though T1-effects of contrast agents are suggested to be reduced at higher fields, quantification of contrast enhancement-to-noise ratio showed a ratio of 4.6 at 7 T and 2.8 at 3T when comparing contrast-to-noise of the mass before and after contrast administration. Both examinations, using a single dose of gadolinium-based contrast agent, achieved good image quality. Final histopathological evaluation showed an invasive ductulolobular carcinoma with an intraductal component. CONCLUSION This initial experience suggests that clinical contrast-enhanced 7 T MRI of the breast is technically feasible and may allow BI-RADS-conform analysis.

Adiabatic multi-echo 31P spectroscopic imaging (AMESING) at 7 T for the measurement of transverse relaxation times and regaining of sensitivity in tissues with short T2* values

An adiabatic multi‐echo spectroscopic imaging (AMESING) sequence, used for 31P MRSI, with spherical k‐space sampling and compensated phase‐encoding gradients, was implemented on a whole‐body 7‐T MR system. One free induction decay (FID) and up to five symmetric echoes can be acquired with this sequence. In tissues with low T2* and high T2, this can theoretically lead to a potential maximum signal‐to‐noise ratio (SNR) increase of almost a factor of three, compared with a conventional FID acquisition with Ernst‐angle excitation. However, with T2 values being, in practice, ≤400 ms, a maximum enhancement of approximately two compared with low flip Ernst‐angle excitation should be feasible. The multi‐echo sequence enables the determination of localized T2 values, and was validated with 31P three‐dimensional MRSI on the calf muscle and breast of a healthy volunteer, and subsequently applied in a patient with breast cancer. The T2 values of phosphocreatine, phosphodiesters (PDE) and inorganic phosphate in calf muscle were 193 ± 5 ms, 375 ± 44 ms and 96 ± 10 ms, respectively, and the apparent T2 value of γ‐ATP was 25 ± 6 ms. A T2 value of 136 ± 15 ms for inorganic phosphate was measured in glandular breast tissue of a healthy volunteer. The T2 values of phosphomonoesters (PME) and PDE in breast cancer tissue (ductulolobular carcinoma) ranged between 170 and 210 ms, and the PME to PDE ratios were calculated to be phosphoethanolamine/glycerophosphoethanolamine = 2.7, phosphocholine/glycerophosphocholine = 1.8 and PME/PDE = 2.3. Considering the relatively short T2* values of the metabolites in breast tissue at 7 T, the echo spacing can be short without compromising spectral resolution, whilst maximizing the sensitivity. Copyright

Detection of alterations in membrane metabolism during neoadjuvant chemotherapy in patients with breast cancer using phosphorus magnetic resonance spectroscopy at 7 Tesla

Here we investigate the feasibility of tumor metabolism monitoring in T1c to T3 breast cancer during neoadjuvant chemotherapy by means of phosphorus (31P) magnetic resonance spectroscopy at 7 tesla (T). Five breast cancer patients were examined using a 31P MRSI sequence, prior to-, halfway-, and after neoadjuvant chemotherapy. The 31P MRSI data were analyzed on group and individual level and compared to a spectrum of a group of healthy volunteers. Ratios of phosphomonoesters (PME) to phosphodiesters (PDE) and phosphomonoesters to inorganic phosphate (Pi) were determined. Histopathologic assessment showed four partial responders and one complete responder to chemotherapy. The 31P spectrum of the patient group was distinctly different from the 31P spectrum of healthy volunteers and transformed its shape during the course of chemotherapy towards the shape of the spectrum of the healthy volunteers. Prior to chemotherapy the PME to PDE signal ratio and the PME to Pi signal ratio were high, and during the course of the chemotherapy these ratios normalized to the value of the healthy volunteers. Metabolite T2 values in tumor tissue tended to be lower than those for healthy glandular tissue. Assessment of individual patients showed that four out of five had a significant drop of the PME to Pi ratio by a factor of 2 or more. On average, the pH of the tumor, calculated from chemical shift variation of Pi, was 0.19 units lower before chemotherapy. We have demonstrated that the sensitivity of 31P MRSI in breast cancer at 7 T is sufficient to detect alterations in membrane metabolism during neoadjuvant chemotherapy, which may be used for early assessment of treatment efficacy.

Proton and phosphorus magnetic resonance spectroscopy of the healthy human breast at 7 T

In vivo water‐ and fat‐suppressed 1H magnetic resonance spectroscopy (MRS) and 31P magnetic resonance adiabatic multi‐echo spectroscopic imaging were performed at 7 T in duplicate in healthy fibroglandular breast tissue of a group of eight volunteers. The transverse relaxation times of 31P metabolites were determined, and the reproducibility of 1H and 31P MRS was investigated. The transverse relaxation times for phosphoethanolamine (PE) and phosphocholine (PC) were fitted bi‐exponentially, with an added short T2 component of 20 ms for adenosine monophosphate, resulting in values of 199 ± 8 and 239 ± 14 ms, respectively. The transverse relaxation time for glycerophosphocholine (GPC) was also fitted bi‐exponentially, with an added short T2 component of 20 ms for glycerophosphatidylethanolamine, which resonates at a similar frequency, resulting in a value of 177 ± 6 ms. Transverse relaxation times for inorganic phosphate, γ‐ATP and glycerophosphatidylcholine mobile phospholipid were fitted mono‐exponentially, resulting in values of 180 ± 4, 19 ± 3 and 20 ± 4 ms, respectively. Coefficients of variation for the duplicate determinations of 1H total choline (tChol) and the 31P metabolites were calculated for the group of volunteers. The reproducibility of inorganic phosphate, the sum of phosphomonoesters and the sum of phosphodiesters with 31P MRS imaging was superior to the reproducibility of 1H MRS for tChol. 1H and 31P data were combined to calculate estimates of the absolute concentrations of PC, GPC and PE in healthy fibroglandular tissue, resulting in upper limits of 0.1, 0.1 and 0.2 mmol/kg of tissue, respectively.

Glycerophosphocholine and Glycerophosphoethanolamine Are Not the Main Sources of the In Vivo (31)P MRS Phosphodiester Signals from Healthy Fibroglandular Breast Tissue at 7 T.

Purpose The identification of the phosphodiester (PDE) 31P MR signals in the healthy human breast at ultra-high field. Methods In vivo 31P MRS measurements at 7 T of the PDE signals in the breast were performed investigating the chemical shifts, the transverse- and the longitudinal relaxation times. Chemical shifts and transverse relaxation times were compared with non-ambiguous PDE signals from the liver. Results The chemical shifts of the PDE signals are shifted −0.5 ppm with respect to glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE), and the transverse and longitudinal relaxation times for these signals are a factor 3 to 4 shorter than expected for aqueous GPC and GPE. Conclusion The available experimental evidence suggests that GPC and GPE are not the main source of the PDE signals measured in fibroglandular breast tissue at 7 T. These signals may predominantly originate from mobile phospholipids.

Detecting breast microcalcifications with high‐field MRI

The aim of this study was to detect microcalcifications in human whole breast specimens using high‐field MRI. Four mastectomy specimens, obtained with approval of the institutional review board, were subjected to gradient‐echo MRI acquisitions on a high‐field MR scanner. The phase derivative was used to detect microcalcifications. The echo time and imaging resolution were varied to study the sensitivity of the proposed method. Computed tomography images of the mastectomy specimens and prior acquired mammography images were used to validate the results. A template matching algorithm was designed to detect microcalcifications automatically. The three spatial derivatives of the signal phase surrounding a field‐perturbing object allowed three‐dimensional localization, as well as the discrimination of diamagnetic field‐perturbing objects, such as calcifications, and paramagnetic field‐perturbing structures, e.g. blood. A longer echo time enabled smaller disturbances to be detected, but also resulted in shading as a result of other field‐disturbing materials. A higher imaging resolution increased the detection sensitivity. Microcalcifications in a linear branching configuration that spanned over 8 mm in length were detected. After manual correction, the automatic detection tool identified up to 18 microcalcifications within the samples, which was in close agreement with the number of microcalcifications found on previously acquired in vivo mammography images. Microcalcifications can be detected by MRI in human whole breast specimens by the application of phase derivative imaging. Copyright

Magnetic resonance imaging and brain injury in the chronic phase after aneurysmal subarachnoid hemorrhage: A systematic review.

Background Case-fatality rates after aneurysmal subarachnoid hemorrhage have decreased over the past decades. However, many patients who survive an aneurysmal subarachnoid hemorrhage have long-term functional and cognitive impairments. Aims We sought to review all data on conventional brain MRI obtained in the chronic phase after aneurysmal subarachnoid hemorrhage to (1) analyze the proportion of patients with cerebral infarction or brain volume changes; (2) investigate baseline determinants predictive of MRI-detected damage; and (3) assess if brain damage is predictive of patient outcome. Summary of review All original data published between 1 January 2000 and 4 October 2017 was searched using the PUBMED, EMBASE, and Web of Science databases. Based on preset inclusion criteria, 15 from 5200 articles were included with a total of 996 aneurysmal subarachnoid hemorrhage patients. Quality assessment, risk of bias assessment, and level of evidence assessment were performed. The results according to aim, with levels of evidence, were: (1) 25 to 81% of aneurysmal subarachnoid hemorrhage patients show infarcts (strong); there is a higher ratio of cerebrospinal fluid-to-intracranial volume in patients compared to controls (strong); (2) there is a negative relation between age (moderate), DCI (low) and brain volume measurement outcomes; (3) lower brain parenchymal volume (strong) and the presence of infarcts or infarct volumes (moderate) are associated with a worse outcome. Conclusion Patients after aneurysmal subarachnoid hemorrhage may demonstrate brain infarcts and decreased brain parenchyma, which is related to worse outcome. Thereby, both brain infarcts and brain volume measurements could be used as outcome markers in pharmaceutical trials. Systematic Review Registration PROSPERO CRD42016040095

Erratum to: Dynamic contrast-enhanced breast MRI at 7T and 3T: an intra-individual comparison study

[This corrects the article DOI: 10.1186/s40064-015-1654-7.].