Yusuke Inoue

Diffusion-weighted Imaging of the Breast: Principles and Clinical Applications

Diffusion-weighted imaging provides a novel contrast mechanism in magnetic resonance (MR) imaging and has a high sensitivity in the detection of changes in the local biologic environment. A significant advantage of diffusion-weighted MR imaging over conventional contrast material-enhanced MR imaging is its high sensitivity to change in the microscopic cellular environment without the need for intravenous contrast material injection. Approaches to the assessment of diffusion-weighted breast imaging findings include assessment of these data alone and interpretation of the data in conjunction with T2-weighted imaging findings. In addition, the analysis of apparent diffusion coefficient (ADC) value can be undertaken either in isolation or in combination with diffusion-weighted and T2-weighted imaging. Most previous studies have evaluated ADC value alone; however, overlap in the ADC values of malignant and benign disease has been observed. This overlap may be partly due to selection of b value, which can influence the concomitant effect of perfusion and emphasize the contribution of multicomponent model influences. The simultaneous assessment of diffusion-weighted and T2-weighted imaging data and ADC value has the potential to improve specificity. In addition, the use of diffusion-weighted imaging in a standard breast MR imaging protocol may heighten sensitivity and thereby improve diagnostic accuracy. Standardization of diffusion-weighted imaging parameters is needed to allow comparison of multicenter studies and assessment of the clinical utility of diffusion-weighted imaging and ADC values in breast evaluation.

Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae

ABSTRACT To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection.

Anti-1-Amino-3-18F-Fluorocyclobutane-1-Carboxylic Acid: Physiologic Uptake Patterns, Incidental Findings, and Variants That May Simulate Disease

Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (18F-FACBC) is a synthetic amino acid analog PET radiotracer undergoing clinical trials for the evaluation of prostate and other cancers. We aimed to describe common physiologic uptake patterns, incidental findings, and variants in patients who had undergone 18F-FACBC PET. Methods: Sixteen clinical trials involving 611 18F-FACBC studies from 6 centers, which included dosimetry studies on 12 healthy volunteers, were reviewed. Qualitative observations of common physiologic patterns, incidental uptake, and variants that could simulate disease were recorded and compared with similar observations in studies of the healthy volunteers. Quantitative analysis of select data and review of prior published reports and observations were also made. Results: The liver and pancreas demonstrated the most intense uptake. Moderate salivary and pituitary uptake and variable mild to moderate bowel activity were commonly visualized. Moderate bone marrow and mild muscle activity were present on early images, with marrow activity decreasing and muscle activity increasing with time. Brain and lungs demonstrated activity less than blood pool. Though 18F-FACBC exhibited little renal excretion or bladder uptake during the clinically useful early imaging time window, mild to moderate activity might accumulate in the bladder and interfere with evaluation of adjacent prostate bed and seminal vesicles in 5%–10% of patients. Uptake might also occur from benign processes such as infection, inflammation, prostatic hyperplasia, and metabolically active benign bone lesions such as osteoid osteoma. Conclusion: Common physiologic uptake patterns were similar to those noted in healthy volunteers. The activity in organs followed the presence of amino acid transport and metabolism described with other amino acid–based PET radiotracers. As with other PET radiotracers such as 18F-FDG, focal nonphysiologic uptake may represent incidental malignancy. Uptake due to benign etiologies distinct from physiologic background also occurred and could lead to misinterpretations if the reader is unaware of them.

Baseline cardiac magnetic resonance imaging versus baseline endomyocardial biopsy for the prediction of left ventricular reverse remodeling and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy.

Endomyocardial biopsy (EMB) and late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging performed at baseline are both used to evaluate the extent of myocardial fibrosis. However, no study has directly compared the effectiveness of these diagnostic tools in the prediction of left ventricular reverse remodeling (LVRR) and prognosis in response to therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Seventy-five patients with newly diagnosed IDCM who were undergoing optimal therapy were assessed at baseline using LGE-CMR imaging and EMB; the former measured LGE area and the latter measured collagen volume fraction (CVF) as possible predictive indices of LVRR and cardiac event-free survival. Among all the baseline primary candidate factors with P < 0.2 as per univariate analysis, multivariate analysis indicated that only LGE area was an independent predictor of subsequent LVRR (β = 0.44; 95 % confidence interval (CI) 0.87–2.53; P < 0.001), as indicated by decreasing left ventricular end-systolic volume index over the 1-year follow-up. Kaplan–Meier curves indicated significantly lower cardiac event-free survival rates in patients with LGE at baseline than in patients without (P < 0.01). By contrast, there was no significant difference in prognosis between patients with CVF values above (severe fibrosis) and below (mild fibrosis) the median of 4.9 %. Cox proportional hazard analysis showed that LGE area was an independent predictor of subsequent cardiac events (hazard ratio 1.06; 95 % CI 1.02–1.10; P ≤ 0.01). The degree of myocardial fibrosis estimated by baseline LGE-CMR imaging, but not that estimated by baseline EMB, can predict LVRR and cardiac event-free survival in response to therapy in patients with newly diagnosed IDCM.

Phase I clinical study of NMK36: a new PET tracer with the synthetic amino acid analogue anti-[18F]FACBC

ObjectiveNMK36 is a novel PET tracer containing a synthetic amino acid analogue anti-[18F]FACBC as the active ingredient, and is under development for the use of tumor diagnosis. A Phase I clinical study of NMK36 was conducted to evaluate its safety, biodistribution, and radiation dosimetry in healthy volunteers.MethodsSix healthy volunteers (Japanese male) received a bolus injection of NMK36 (174.4–201.4xa0MBq) intravenously. The safety of NMK36 was evaluated by monitoring signs/symptoms, electrocardiography, recording vital signs, and laboratory examinations at baseline and several time points in 6xa0days after injection. A total of 11 whole-body PET-CT scans were acquired up to 4xa0h post-injection, and venous blood and urine samples were also collected for 6 and 24xa0h post-injection, respectively. Based on the results of the biodistribution study, absorbed radiation dose was estimated by the MIRD method.ResultsAlthough two adverse events occurred after the injection of NMK36, they were mild and disappeared without any specific treatment. NMK36 preferentially accumulated in the pancreas and liver early after injection, followed by rapid clearance from the pancreas. Persistent uptake was observed in the skeletal muscle. NMK36 showed low uptake in the brain, and its urinary excretion was limited (5.40xa0±xa01.43% of the injected dose at 24xa0h post-injection). The liver was the critical organ, with a mean absorbed dose of 40.6xa0μGy/MBq. The estimated effective dose of NMK36 was 13.8xa0μSv/MBq, which was similar to or lower than those of radiotracers approved for clinical use including [18F]FDG.ConclusionsThe findings of this study indicate that NMK36 is well tolerated. NMK36 has favorable characteristics for imaging brain and pelvic tumors, such as low brain uptake, slow urinary excretion, and high in vivo stability.

Source analysis of stimulus-preceding negativity constrained by functional magnetic resonance imaging.

The stimulus-preceding negativity (SPN) is an event-related potential (ERP) reflecting anticipation. The anterior insular cortex is assumed to be one of the physiological sources of the SPN. However, the precise neural substrates of the SPN have yet to be confirmed. We therefore performed separate functional magnetic resonance imaging (fMRI) and ERP studies using the same time estimation task, followed by fMRI-constrained ERP source analysis. Dipole locations were determined by the fMRI results, while the time courses of dipole activities were modeled by the ERP data. Analysis revealed that the right anterior insula was significantly activated before delivery of the feedback stimulus, whereas the left anterior insula was not, and that the SPN mainly arose from four groups of brain regions related to, respectively: (1) the salience network, (2) reward expectation, (3) perceptual anticipation, and (4) arousal. The results suggest that the SPN pertains to multiple brain functions with complex interactions.

Acquisition Protocols and Correction Methods for Estimation of the Heart-to-Mediastinum Ratio in 123I-Metaiodobenzylguanidine Cardiac Sympathetic Imaging

Septal penetration of high-energy photons affects quantitative results in imaging of 123I-labeled tracers. We investigated acquisition protocols (collimator choice and energy window setting) and correction methods for estimating the heart-to-mediastinum (H/M) ratio in cardiac 123I-metaiodobenzylguanidine (MIBG) imaging. Methods: Four hours after 123I-MIBG injection, 40 patients successively underwent planar anterior chest imaging with the medium-energy (ME) (ME method) and low-energy high-resolution (LEHR) (LEHR method) collimators. A 20% energy window was used for both collimators. Another 40 patients were imaged successively with the ME collimator and a 20% window (ME method), the low-medium-energy (LME) collimator and a 20% window (LME20 method), and the LME collimator and a 15% window (LME15 method). The H/M ratios obtained by the LEHR, LME20, and LME15 methods were corrected using their correlations with the H/M ratio obtained by the ME method (empiric correction). The 123I-dual-window (IDW) correction was also applied to remove the influence of high-energy photons. Results: Without correction, severe underestimation of the H/M ratio was shown for the LEHR method using the ME method as a standard, and this underestimation increased with increasing H/M ratios. Underestimation substantially decreased using the LME20 method and further using the LME15 method. Empiric correction reduced the error in the H/M ratio by the LEHR method, but the error was still evident. After empiric correction, the H/M ratios with the LME collimator were comparable to those with the ME collimator. The IDW correction only partially reduced underestimation by the LEHR method and caused a small overestimation for the LME15 method. Conclusion: The use of an LME collimator appears to be acceptable for cardiac 123I-MIBG imaging as an alternative to an ME collimator, and the application of a 15% energy window is recommended when an LME collimator is used. Empiric correction is also expected to improve exchangeability between H/M ratios calculated with ME and LME collimators. Neither the use of an LEHR collimator nor the use of IDW correction is recommended.

Diffusion-weighted imaging of local recurrent prostate cancer after radiation therapy: comparison with 22-core three-dimensional prostate mapping biopsy.

Accurate localization of local recurrence within the prostate gland is important to perform focal salvage therapy effectively with minimal complications. The purpose of this study was to evaluate the usefulness of diffusion-weighted imaging (DWI) in the detection and localization of prostate cancer recurrence in patients with biochemical failure after definitive radiation therapy using 22-core three-dimensional prostate mapping biopsy (3D-PMB) as a standard reference. Ten patients who underwent magnetic resonance imaging and 22-core 3D-PMB were retrospectively analyzed. For visual assessment of DWI, the prostate was divided into 22 regions corresponding to 3D-PMB. Two diagnostic radiologists determined the presence of abnormal high signal intensity in each region on DWI, and the results of DWI were compared with those of 3D-PMB. Of the 220 regions, 16 regions in six patients were positive for cancer on 3D-PMB, and 30 regions in six patients were judged as positive on DWI. On a patient-by-patient basis, sensitivity and specificity were 100% (6/6) and 100% (4/4), respectively. On a region-by-region basis, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 69% (11/16), 91% (185/204), 37% (11/30), 97% (185/190) and 89% (196/220), respectively. For discrepant localization between DWI and pathology, DWI-positive and pathology-positive regions tended to be adjacent to each other. In conclusion, DWI is a useful tool for the detection and localization of recurrent prostate cancer in patients with biochemical failure after radiation therapy and may be helpful in the planning of focal salvage therapy.

Usefulness of the navigator-echo triggering technique for free-breathing three-dimensional magnetic resonance cholangiopancreatography

PURPOSEnTo prospectively compare the navigator-echo triggering technique (navigator technique) and the conventional respiratory triggering technique using bellows (bellows technique) for free-breathing three-dimensional (3D) magnetic resonance cholangiopancreatography (MRCP) under clinical conditions.nnnMATERIALS AND METHODSnForty patients referred for evaluation of biliary or pancreatic diseases underwent 3D MRCP examination using both navigator and bellows techniques. Two independent radiologists visually evaluated the image quality of 12 segments of the pancreaticobiliary tree in a blinded manner. In addition, the clarity of the lesion was compared between the two techniques in a side-by-side manner.nnnRESULTnMRCP images were successfully acquired using both techniques in all patients. No significant difference in acquisition time was found between the two techniques. The image quality was significantly better using the navigator technique than using the bellows technique for the following seven segments: the head, body, and tail of the pancreatic duct; right hepatic duct; anterior and posterior segments of the right hepatic duct; and cystic duct. The other segments (common hepatic and bile duct, left hepatic duct, medial and lateral segments of left hepatic duct, gallbladder) showed no significant difference. The clarity of lesion depiction was significantly better using the navigator technique than using the bellows technique.nnnCONCLUSIONnRespiratory-triggered 3D MRCP using the navigator technique was shown to be feasible in routine clinical practice. The navigator technique improved the image quality of free-breathing 3D MRCP compared with the bellows technique. The clarity of lesion visualization was also better using the navigator technique than using the bellows technique.

EORTC QLQ-BM22 and QLQ-C30 quality of life scores in patients with painful bone metastases of prostate cancer treated with strontium-89 radionuclide therapy

PurposeApproximately 80xa0% of patients with prostate cancer will develop bone metastases, which often lead to bone pain and skeletal-related events. Sr-89 is an established alternative for the palliation of bone pain in prostate cancer. We aimed to assess the effect of Sr-89 radionuclide therapy on quality of life (QOL) in prostate cancer patients with painful bone metastases.Materials and methodsThirteen patients received a single intravenous injection of Sr-89 at a dose of 2.0xa0MBq/kg. All patients underwent QOL evaluation prior to Sr-89 treatment and 1, 2, and 3xa0months afterward using the Japanese version of the EORTC QLQ-BM22, EORTC QLQ-C30, a VAS, and face scale. We also evaluated PSA and ALP response and toxicity of the Sr-89 therapy.ResultsThe pain characteristics subscale of the EORTC QLQ-BM22 was significantly reduced from 1xa0month onward compared with the baseline. The functional interference and psychosocial aspects subscales were significantly higher than baseline from 2xa0months onward. At 2xa0months, VAS indicated a significant reduction in pain as compared to the baseline. Sr-89 therapy caused a nonsignificant reduction in PSA and ALP levels. No patients had leukocyte toxicity, and one patient had grade 3 platelet toxicity.ConclusionSr-89 radionuclide therapy can provide not only reduced pain characteristics but also better psychosocial aspects and functional interference in patients with painful bone metastases of prostate cancer.