Since the first pioneering report of hyperpolarized [1-¹³C]pyruvate magnetic resonance imaging (MRI) of the Warburg effect in prostate cancer patients, clinical dissemination of the technique has been rapid; close to 10 sites worldwide now possess a polarizer fit for the clinic, and more than 30 clinical trials, predominantly for oncological applications, are already registered on the US and European clinical trials databases. Hyperpolarized ¹³C probes to study pathophysiological processes beyond the Warburg effect, including tricarboxylic acid cycle metabolism, intra-cellular pH and cellular necrosis have also been demonstrated in the preclinical arena and are pending clinical translation, and the simultaneous injection of multiple co-polarized agents is opening the door to high-sensitivity, multi-functional molecular MRI with a single dose. Here, we review the biomedical applications to date of the two polarization methods that have been used for in vivo hyperpolarized ¹³C molecular MRI; namely, dissolution dynamic nuclear polarization and parahydrogen-induced polarization. The basic concept of hyperpolarization and the fundamental theory underpinning these two key ¹³C hyperpolarization methods, along with recent technological advances that have facilitated biomedical realization, are also covered.

Hemangioblastomas of the cerebellopontine angle (CPA) that emerge extra-axially from the peripheral nervous system are extremely rare. We report a case of hemangioblastoma of the CPA evaluated by pseudocontinuous arterial spin labeling (pCASL). The high rate of tumor blood flow determined using pCASL provided additional useful information for the differential diagnosis of the CPA tumors in this patient.

Purpose: To investigate the influence of microcystic, elongated and fragmented (MELF) pattern invasion on preoperative evaluation of lymph node (LN) metastasis and myometrial invasion in patients with low-grade endometrial carcinoma.

Methods: The study included 192 consecutive patients with low-grade endometrial carcinoma who underwent preoperative computed tomography (CT) and magnetic resonance imaging (MRI), followed by surgery. One hundred sixty one of 192 patients underwent LN dissection and were analyzed for LN metastasis. All patients were analyzed for myometrial invasion. Presence of enlarged LN was evaluated by using size criteria on CT. Depth of myometrial invasion was evaluated on MRI using T₂-weighted imaging, diffusion-weighted imaging and contrast-enhanced T₁-weighted imaging comprehensively. Sensitivity and specificity for LN metastasis and deep myometrial invasion were evaluated for MELF group and non-MELF group. The difference of sensitivity between two groups was compared using Chi-square and Fisher’s exact test.

Results: MELF pattern invasion was identified in 43/192 patients (22%). LN metastases were observed in 18/39 patients in MELF group and 6/122 patients in non-MELF group for pelvic LN and 11/29 patients in MELF group and 4/57 patients in non-MELF group for para-aortic LN. Sensitivity for the detection of pelvic LN metastasis in MELF group was significantly lower than in non-MELF group (16.7% vs 66.7%). As for the assessment of the deep myometiral invasion, pathological deep myometrial invasion were found in 31/43 patients in MELF group and 32/149 patients in non-MELF group. Sensitivity in MELF group showed lower values than in non-MELF group (54.8% vs 78.1% for reader 1, 54.8% vs 62.5% for reader 2), although there was no statistically significant difference (P = 0.09 for reader 1 and P = 0.72 for reader 2).

Conclusion: In case of low-grade endometrial carcinoma with MELF pattern invasion, preoperative staging by CT and MRI have a risk for underestimation.

Purpose: To correlate peritumoral fat content using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with histologic prognostic factors in breast carcinoma.

Materials and Methods: This study consisted of 100 patients who were diagnosed with invasive carcinoma of breast and underwent breast MRI including IDEAL before surgery. The scan time of IDEAL fat fraction (FF) map imaging was 33 s. Four regions of interests (ROIs), which are a distance of 5 mm from the tumor edge, and one ROI in the mammary fat of the healthy side were set on the FF map. Then average peritumoral FF values (FFt), average FF values in the healthy side (FFh), and peritumoral fat ratio (pTFR: defined as FFt/FFh) were calculated. Histologically, the presence of lymph node metastasis and the MIB-1 index were evaluated.

Results: FFt and pTFR for breast carcinoma with lymph node metastasis (79.27 ± 10.36 and 0.897 ± 0.078) were significantly lower than those without (86.23 ± 4.53 and 0.945 ± 0.032) (P < 0.001 and P = 0.005). Spearman rank correlation suggested that the FFt correlated with the MIB-1 index (r = −340, P = 0.001).

Conclusion: Quantification of peritumoral fat using IDEAL-iron quantification is associated with the histologic prognostic factors, and may be a practical tool for therapeutic strategy of breast carcinoma.

Purpose: Although there is no lymphatic system in the central nervous system (CNS), there seems to be a mechanism to remove macro molecules from the brain. Cerebrospinal fluid (CSF) and interstitial fluid (ISF) are thought to be parts of this pathway, but the details are not known. In this study, MR signal of the extracellular water was decomposed into components with distinct T₂’s, to obtain some information about distribution of waste material in the brain.

Methods: Images were acquired using a Curr, Purcell, Meiboom, Gill (CPMG) imaging sequence. In order to reduce T₁ contamination and the signal oscillation, hard pulses were used as refocusing pulses. The signal was then decomposed into many T₂ components using non-negative least squares (NNLS) in pixel-by-pixel basis. Finally, a color map was generated by assigning different color for each T₂ component, then adding them together.

Results: From the multi-echo images, it was possible to decompose the decaying signal into separate T₂ components. By adjusting the color table to create the color map, it is possible to visualize the extracellular water distribution, as well as their T₂ values. Several observation points include: (1) CSF inside ventricles has very long T₂ (~2 s), and seems to be relatively homogeneous, (2) subarachnoid CSF also have long T₂, but there are short T₂ component at the brain surface, at the surface of dura, at the blood vessels in the subarachnoid space, etc., (3) in the brain parenchyma, short T₂ components (longer than intracellular component but shorter than CSF) exists along the white matter, in the choroid plexus, etc. These can be considered as distribution of macromolecules (waste materials) in the brain.

Conclusion: From T₂ component analysis it is possible to obtain some insight into pathways for the transport of large molecules in the CNS, where no lymphatic system is present.

Purpose: The aim of this study was to investigate whether the detectability of brain volume change in voxel-based morphometry (VBM) with gray matter images is affected by mild white matter lesions (MWLs).

Methods: Three-dimensional T₁-weighted images (3D-T₁WIs) of 11 healthy subjects were obtained using a 3T MR scanner. We initially created 3D-T₁WIs with focal cortical atrophy simulated cortical atrophy in left amygdala (type A) and the left medial frontal lobe (type B) from control 3D-T₁WIs. Next, the following three types of MWL images were created: type A + 1L and type B + 1L images, only one white matter lesion; type A + 4L and type B + 4L images, four white matter lesions at distant positions; and type A + 4L^* and type B + 4L^* images, four white matter lesions at clustered positions. Comparisons between the control group and the other groups were performed with VBM using segmented gray matter images.

Results: The gray matter volume was significantly lower in the type A group than in the control group, and similar results were observed in the type A + 1L, type A + 4L, and type A + 4L^* groups. Additionally, the gray matter volume was significantly lower in the type B group than in the control group, and similar results were observed in the type B + 1L, type B + 4L, and type B + 4L^* groups, but the cluster size in type B + 4L^* was smaller than that in type B.

Conclusion: Our study showed that the detectability of brain volume change in VBM with gray matter images was not decreased by MWLs as lacunar infarctions. Therefore, we think that group comparisons with VBM should be analyzed by groups including and excluding subjects with MWLs, respectively.

Purpose: To determine the optimal combination of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) findings for the diagnosis of hepatocellular carcinoma (HCC) and to compare its diagnostic ability to that of dynamic computed tomography (CT) in patients with chronic liver disease.

Methods: This multi-institutional study consisted of two parts: Study 1, a retrospective study to determine the optimal combination of gadoxetate disodium-enhanced MRI findings (decision tree and logistic model) to distinguish HCC (n = 199) from benign (n = 81) or other malignant lesions (n = 95) (375 nodules in 269 patients) and Study 2, a prospective study to compare the diagnostic ability of gadoxetate disodium-enhanced MRI to distinguish HCC (n = 73) from benign (n = 15) or other malignant lesions (n = 12) with that of dynamic CT (100 nodules in 83 patients). Two radiologists independently evaluated the imaging findings (Study 1 and 2) and made a practical diagnosis (Study 2).

Results: In Study 1, rim or whole enhancement on arterial phase images, signal intensities on T₂-weighted/diffusion-weighted/portal venous/transitional/hepatobiliary phase images, and signal drop on opposed-phase images were independently useful for differential diagnosis. In Study 2, the accuracy, sensitivity, negative predictive value, and negative likelihood ratio of the CT decision tree (reader 2) were higher than those of MRI Model 2 (P = 0.015–0.033). There were no other significant differences in diagnostic ability (P = 0.059–1.000) and radiologist-made practical diagnosis (P = 0.059–1.000) between gadoxetate disodium-enhanced MRI and CT.

Conclusion: We identified the optimal combination of gadoxetate disodium-enhanced MRI findings for HCC diagnosis. However, its diagnostic ability was not superior to that of dynamic CT.

Purpose: To compare the image quality between turbo spin-echo (TSE)-diffusion weighted imaging (DWI) and single-shot echo-planar imaging (EPI)-DWI, and to verify the diagnostic performance of the apparent diffusion coefficient (ADC) parameters of the two techniques by using histogram analysis in terms of differentiation between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions.

Methods: Ninety-four women with 94 lesions diagnosed as breast cancer by surgery underwent IRB-approved preoperative magnetic resonance imaging, including TSE and EPI-DWI with b-values of 50 and 850 s/mm². Twenty lesions were identified as DCIS and 74 as IDC. Image quality [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and geometric distortion] was evaluated quantitatively and compared between the TSE and EPI-DWI. A histogram analysis of the entire tumor voxel-based ADC data was performed, and the 10th, 25th, 50th, 75th, and 90th percentile values of each technique were compared between DCIS and IDC lesions.

Results: The SNR and CNR of TSE-DWI were significantly higher than those of EPI-DWI (P < 0.0001 and < 0.0001). The geometric distortion of TSE-DWI was significantly lower than that of EPI-DWI (P < 0.0001). In TSE-DWI, the 10th, 25th, 50th, and 75th percentile values were significantly different between the DCIS and IDC lesions (P = 0.0010, 0.0004, 0.0008, and 0.0044, respectively). In EPI-DWI, the 50th and 75th percentile values were significantly different between the two groups (P = 0.0009 and 0.0093). There was no significant difference in the area under the curve of the receiver operating characteristic analysis of the 10th, 25th, 50th, and 75th percentile values of TSE-DWI, and the 50th and 75th percentile values of EPI-DWI (P = 0.29).

Conclusion: The image quality of TSE-DWI was better than that of EPI-DWI. DCIS lesions were distinguished from IDC lesions with a wider range of percentile values in TSE-DWI than in EPI-DWI, although diagnostic performance was not significantly different between the techniques.

Purpose: To compare the diagnostic value of mono-exponential, bi-exponential, and stretched exponential diffusion-weighted imaging (DWI) for differentiating benign and malignant hepatic lesions.

Methods: This prospective study was approved by our Institutional Review Board and the patients provided written informed consent. Magnetic resonance imaging was acquired for 56 patients with suspected liver disease. This identified 90 focal liver lesions with a maximum diameter >10 mm, of which 47 were benign and 43 were malignant. Using home-built software, two radiologists measured the DWI parameters of hepatic lesions for three models: the apparent diffusion coefficient (ADC) from a mono-exponential model; the true diffusion coefficient (D), pseudo-diffusion coefficient (D^*), and perfusion fraction (f) from a bi-exponential model; and the distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) from a stretched exponential model. The parameters were compared between benign and malignant hepatic lesions.

Results: ADC, D, D^*, f, and DDC values were significantly lower for malignant hepatic lesions than for benign lesions (P < 0.0001–0.03). Although logistic regression analysis demonstrated that DDC was the only statistically significant parameter for differentiating benign and malignant lesions (P = 0.039), however, the areas under the receiver operating characteristic curve for differentiating benign and malignant lesions were comparable between ADC (0.98) and DDC (0.98) values.

Conclusion: DDC values obtained from the stretched exponential model could be also used as a quantitative imaging biomarker for differentiating benign and malignant hepatic lesions, however, the diagnostic performance was comparable with ADC values.

Purpose: The combination of modified Dixon (mDixon) and periodically rotated overlapping parallel lines with enhanced reconstruction sequence with two interleaved echoes, which promotes uniform fat-suppression and motion insensitivity, has recently become available for commercial magnetic resonance imaging (MRI) scanners. To compare the robustness of this combination sequence with that of standard Cartesian mDixon sequence for fat-suppressed T₂-weighted imaging in clinical head and neck MRI.

Methods: Fifty patients with head and neck tumors were involved this study. All patients underwent MRI using both the combination and standard sequences. Two radiologists independently scored motion artifacts and water–fat separation error using a 4-point scale (1, unacceptable; 4, excellent). Furthermore, comprehensive comparative evaluation was performed using a 5-point scale (1, substantially inferior; 5, substantially superior). Data were statistically analyzed using the Wilcoxon signed-rank test.

Results: In the motion artifact assessment, ratings of 3 or 4 points were assigned to 45% (observer-1, 58.0%; observer-2, 32.0%) and 97% (100%; 94.0%) of images for the standard and combination sequences, respectively (P < 0.001). For the water–fat separation error assessment, ratings of 3 or 4 points were assigned to 100% (100%; 100%) and 85% (84.0%; 86.0%) of images, respectively (P < 0.001). In the comprehensive evaluation, of the 100 cases (observer-1, 50; observer-2, 50), 96 were rated at four or five points. In cases with slight or no motion artifacts and water–fat separation errors, the combination sequence was superior to the standard sequence in term of noise and sharpness, and equal in terms of contrast.

Conclusion: Although water–fat separation errors increased significantly in the combination sequence, most of these were acceptable. The significantly decreased motion artifacts in the combination sequence significantly improved image quality overall.

Purpose: Neuropathic pain is a complex and distressing chronic illness in modern medicine. Since 1990s, motor cortex stimulation (MCS) has emerged as a potential treatment for chronic neuropathic pain; however, the precise mechanisms underlying analgesia induced by MCS are not completely understood. The purpose of the present study was to investigate the blood oxygen-level dependent (BOLD) response in the brain during MCS.

Methods: We inserted a bipolar tungsten electrode into the primary motor cortex (M1) of adult male Wistar rats. Functional magnetic resonance imaging (fMRI) scans were implemented simultaneously with the electrical stimulation of M1 and the BOLD signals taken from the fMRI were used as an index to reflect the response against MCS.

Results: Our results demonstrated that the bilateral M1, ipsilateral caudate-putamen, and ipsilateral primary somatosensory cortex to the stimulation spot were activated after the onset of MCS. The BOLD signal time courses were analysed in these regions and similar temporal characteristics were found.

Conclusion: By conducting direct cortical stimulation of the rodent brain to investigate its instant effect using fMRI, we identified encephalic regions directly involved in the instant motor cortical stimulation effects in healthy rat models. This result may be essential in establishing a foundation for further research on the underlying neuropathways associated with the MCS effects.

Purpose: To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF).

Methods: Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T₁ and T₂ values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance.

Results: The signal intensity on the 3D-real IR image in each CSF region peaked at 4 h, and was decreased significantly by 24 h (P< 0.05). All patients had a maximum signal intensity at 4 h in the CPA, and Syl. The mean CPL signal intensity peaked at 4 h and decreased significantly by 24 h (P < 0.05). All patients but two had a maximum signal intensity at 4 h. Regarding the T₁ value in the cerebellar WM and GM, the T₁ value at 10 min post-IV-GBCA was significantly decreased compared to the pre-contrast scan, but no significant difference was observed at the other time points. There was no significant change in T₂ in the gray or white matter at any of the time points.

Conclusion: Time course of GBCA after IV-SD-GBCA could be evaluated by 3D-real IR imaging in CSF spaces and in the brain by MRF.

To accelerate high-resolution diffusion-weighted imaging with a multi-shot echo-planar sequence, we propose an approach based on reduced averaging and deep learning. Denoising convolutional neural networks can reduce amplified noise without requiring extensive averaging, enabling shorter scan times and high image quality. The preliminary experimental results demonstrate the superior performance of the proposed denoising method over state-of-the-art methods such as the widely used block-matching and 3D filtering.

Not only magnetization transfer contrast (MTC) pulse, but also chemical shift selective (CHESS) pulse would be a useful additional one for shortening the scan time of neuromelanin imaging. We compared three sequences among turbo-spin echo (TSE) images with CHESS, MTC, and without an additional pulse in the same short time, 3 min 20 s. The TSE with CHESS image was the most useful for the diagnosis of neuromelanin within the limited time.

The feasibility of the 3D dynamic improved motion-sensitized driven-equilibrium steady-state free precession (3D dynamic iMSDE SSFP) was evaluated for visualizing CSF motion and the appropriate parameters were determined. Both flow phantom and volunteer studies revealed that linear ordering and the shortest acquisition duration time were optimal. 3D dynamic iMSDE SSFP provides good quality imaging of CSF motion in the whole brain and enables visualization of flow in arbitrary planes from a single 3D volume scan.

T₂-fluid-attenuated inversion recovery images (FLAIR) mismatch sign is now known to be a specific yet insensitive image feature for IDH-mutant, 1p19q non-codeleted astrocytoma. The current study revealed that lesion presenting T₂-FLAIR mismatch exhibited extremely long T₁- and T₂-relaxation time while T₂-FLAIR matched lesions showed low to moderate values. On the other hand, IDH-wildtype tumors presented noticeably short T₁- and T₂-relaxation time. These different relaxation time characteristics seemed to render T₂-FLAIR mismatch sign of becoming such a unique and specific image feature for IDH-mutant, 1p19q non-codeleted astrocytoma.