Toward Ultra-high-quality-factor Wireless Masing Magnetic Resonance Sensing.

It has been recently shown that a bolus of hyperpolarized nuclear spins can yield stimulated emission signals similar in nature to that of maser, potentially enabling new ways of sensing of hyperpolarized contrast media, including most notably [1-13C]pyruvate that is under evaluation in over 50 clinical trials for metabolic imaging of cancer. The stimulated NMR signal emissions lasting for minutes do not require radio-frequency excitation, offering unprecedented advantages compared to conventional MR sensing. However, creating nuclear spin maser emission is challenging in practice due to stringent fundamental requirements, making practical in vivo applications hardly possible using conventional passive MR detectors. Here, we demonstrate the utility of a wireless NMR maser detector, the quality factor of which was enhanced 22-fold (to 1,670) via parametric pumping. This active-feedback technique breaks the intrinsic fundamental limit of NMR detector circuit quality factor. We show the use of parametric pumping to reduce the threshold requirement for inducing nuclear spin masing at 300 MHz resonance frequency in preclinical MRI scanner. Indeed, stimulated emission from hyperpolarized protons was obtained under highly unfavorable conditions of low magnetic field homogeneity (T2* of 3 ms). Greater gains of the quality factor of MR detector (up to 1 million) were demonstrated.

Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation of the Hyperpolarized Ketone and Hemiketal Forms of Allyl [1-13C]Pyruvate.

13C hyperpolarized pyruvate is an emerging MRI contrast agent for sensing molecular events in cancer and other diseases with aberrant metabolic pathways. This metabolic contrast agent can be produced via several hyperpolarization techniques. Despite remarkable success in research settings, widespread clinical adoption faces substantial roadblocks because the current sensing technology utilized to sense this contrast agent requires the excitation of 13C nuclear spins that also need to be synchronized with MRI field gradient pulses. Here, we demonstrate sensing of hyperpolarized allyl [1-13C]pyruvate via the stimulated emission of radiation that mitigates the requirements currently blocking broader adoption. Specifically, 13C Radiofrequency Amplification by Stimulated Emission of Radiation (13C RASER) was obtained after pairwise addition of parahydrogen to a pyruvate precursor, detected in a commercial inductive detector with a quality factor (Q) of 32 for sample concentrations as low as 0.125 M with 13C polarization of 4%. Moreover, parahydrogen-induced polarization allowed for the preparation of a mixture of ketone and hemiketal forms of hyperpolarized allyl [1-13C]pyruvate, which are separated by 10 ppm in 13C NMR spectra. This is a good model system to study the simultaneous 13C RASER signals of multiple 13C species. This system models the metabolic production of hyperpolarized [1-13C]lactate from hyperpolarized [1-13C]pyruvate, which has a similar chemical shift difference. Our results show that 13C RASER signals can be obtained from both species simultaneously when the emission threshold is exceeded for both species. On the other hand, when the emission threshold is exceeded only for one of the hyperpolarized species, 13C stimulated emission is confined to this species only, therefore enabling the background-free detection of individual hyperpolarized 13C signals. The reported results pave the way to novel sensing approaches of 13C hyperpolarized pyruvate, potentially unlocking hyperpolarized 13C MRI on virtually any MRI system─an attractive vision for the future molecular imaging and diagnostics.

New Horizons in Hyperpolarized 13C MRI.

Hyperpolarization techniques significantly enhance the sensitivity of magnetic resonance (MR) and thus present fascinating new directions for research and applications with in vivo MR imaging and spectroscopy (MRI/S). Hyperpolarized 13C MRI/S, in particular, enables real-time non-invasive assessment of metabolic processes and holds great promise for a diverse range of clinical applications spanning fields like oncology, neurology, and cardiology, with a potential for improving early diagnosis of disease, patient stratification, and therapy response assessment. Despite its potential, technical challenges remain for achieving clinical translation. This paper provides an overview of the discussions that took place at the international workshop "New Horizons in Hyperpolarized 13C MRI," in March 2023 at the Bavarian Academy of Sciences and Humanities, Munich, Germany. The workshop covered new developments, as well as future directions, in topics including polarization techniques (particularly focusing on parahydrogen-based methods), novel probes, considerations related to data acquisition and analysis, and emerging clinical applications in oncology and other fields.

Super-resolution Reflection Microscopy via Absorbance Modulation.

In recent years, fluorescence microscopy has been revolutionized. Reversible switching of fluorophores has enabled circumventing the limits imposed by diffraction. Thus, resolution down to the molecular scale became possible. However, to the best of our knowledge, the application of the principles underlying super-resolution fluorescence microscopy to reflection microscopy has not been experimentally demonstrated. Here, we present the first evidence that this is indeed possible. A layer of photochromic molecules referred to as the absorbance modulation layer (AML) is applied to a sample under investigation. The AML-coated sample is then sequentially illuminated with a one-dimensional (1D) focal intensity distribution (similar to the transverse laser mode TEM01) at wavelength λ1 = 325 nm to create a subwavelength aperture within the AML, followed by illumination with a Gaussian focal spot at λ2 = 633 nm for high-resolution imaging. Using this method, called absorbance modulation imaging (AMI) in reflection, we demonstrate a 2.4-fold resolution enhancement over the diffraction limit for a numerical aperture (NA) of 0.65 and wavelength (λ) of 633 nm.

Solid pseudopapillary neoplasms of the pancreas in childhood and adolescence-an analysis of the German Registry for Rare Pediatric Tumors (STEP).

Solid pseudopapillary neoplasms (SPNs) are the most common entity among pediatric pancreatic tumors. Still, these are rare tumors with an annual incidence of 0.1-0.2/1,000,000, and little is known about their optimal treatment. This analysis aimed to increase knowledge about the occurrence and treatment strategies of SPN in childhood. Data regarding diagnostics, treatment, and outcome of children aged 0-18 years with SPN recorded in the German Registry for Rare Pediatric Tumors (STEP) were analyzed. Thirty-eight patients were identified with a median age of 14.5 years at diagnosis (range: 8-18) and a female preponderance (81.6%). The most frequent location of the tumor was the pancreatic tail. In histopathological and immunohistochemical examination, pseudopapillary, solid, and cystic lesions as well as expression of beta-catenin, progesterone receptors, and cyclin D1 were the most common findings. All patients underwent surgical resection. Most patients underwent open resection, predominantly tail resection for tumors in the tail region and pylorus-preserving pancreaticoduodenectomy for tumors in the head region. The main postoperative sequela was exogenous pancreatic insufficiency (23.7%), especially with SPN in the pancreatic head. No recurrence occurred during follow-up, although two patients underwent resection with microscopic residue. CONCLUSION: SPN of the pancreas in childhood are low-grade malignancies with usually favorable treatment outcomes. However, therapy can lead to relevant long-term sequelae. To prevent recurrence, complete surgical resection is recommended, sparing as much healthy pancreatic tissue as possible. Interdisciplinary collaboration between specialists is essential to optimize treatment. Molecular genetic analysis of these tumors could improve understanding of their genesis. WHAT IS KNOWN: • Solid pseudopapillary neoplasms (SPNs) of the pancreas are very rare tumors in childhood. • Little is known about tumorigenesis, and there are no specific guidelines for treatment and follow-up in pediatric patients. WHAT IS NEW: • Characteristics, treatment, and outcome were comprehensively assessed in a large cohort of pediatric patients with SPN. • We propose recommendations for diagnosis, treatment, and follow-up of children with SPN, based on our analysis and considering published experience.

The role of surgery in the treatment of neuroblastoma metastases at rare sites.

PURPOSE: Treatment of neuroblastoma metastases usually consists of chemotherapy and irradiation. However, in selected cases, surgical treatment is also indicated. In this study, we present three cases of patients with neuroblastoma metastases at rare sites that underwent surgery. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent surgery for neuroblastoma at our department of Pediatric Surgery and Pediatric Urology at the University Children's Hospital in Tuebingen and selected those patients who had surgery explicitly for a metastasis. RESULTS: Between 2002 and 2020, 277 children underwent surgical treatment for neuroblastoma. Three cases with metastases at exceptional sites are presented here after therapy according to protocols. One patient had a penile metastasis and received surgery including a plastic reconstruction. The patient showed no signs of erectile or urinary dysfunction at follow-up. Another patient had a metastasis in the proximal ulna, which remained vital even after exhausted treatment after two relapses. Afterward there was no restriction of movement of the extremity. The third patient had, amongst others, metastases to the pancreatic body and to the liver. Both were surgically removed during primary tumor resection. This patient died after local tumor relapse. The other two patients showed no evidence of tumor relapse after a follow-up of 18 and 17 months, respectively. CONCLUSION: Although children with neuroblastoma often present with metastases, there is no recommendation for surgical treatment other than diagnostic biopsies. In case of persistence of metastasis or after exhaustion of high-risk therapy, surgical resection must be considered.

In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen.

Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non-invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra-fast and low-cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1-13 C]pyruvate-d3 for injection in 6 minutes. The injected solution was sterile, non-toxic, pH neutral and contained ≈30 mM [1-13 C]pyruvate-d3 polarized to ≈11 % (residual 250 mM methanol and 20 µM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.

Increasing Patient Safety and Treatment Quality by Using Intraoperative MRI for Organ-Preserving Tumor Resection and High-Dose Rate Brachytherapy in Children with Bladder/Prostate and Perianal Rhabdomyosarcoma.

In children with bladder/prostate (BP) and perianal rhabdomyosarcoma (RMS), we use a hybrid treatment concept for those suitable, combining organ-preserving tumor resection and high-dose rate brachytherapy (HDR-BT). This treatment concept has been shown to improve outcomes. However, it is associated with specific challenges for the clinicians. The exact position of the tubes for BT is a prerequisite for precise radiotherapy. It can finally be determined only with an MRI or CT scan. We evaluated the use of an intraoperative MRI (iMRI) to control the position of the BT tubes and for radiotherapy planning in all patients with BP and perianal RMS who received the above-mentioned combination therapy in our department since January 2021. iMRI was used in 12 children. All tubes were clearly localized. No adverse events occurred. In all 12 children, radiotherapy could be started on time. In a historical cohort without iMRI, this was not possible in 3 out of 20 children. The use of iMRI in children with BP and perianal RMS improved patient safety and treatment quality. This technology has proven to be successful for the patient population we have defined and has become a standard procedure in our institution.

Over 20% Carbon-13 Polarization of Perdeuterated Pyruvate Using Reversible Exchange with Parahydrogen and Spin-Lock Induced Crossing at 50 µT.

Carbon-13 hyperpolarized pyruvate is about to become the next-generation contrast agent for molecular magnetic resonance imaging of cancer and other diseases. Here, efficient and rapid pyruvate hyperpolarization is achieved via signal amplification by reversible exchange (SABRE) with parahydrogen through synergistic use of substrate deuteration, alternating, and static microtesla magnetic fields. Up to 22 and 6% long-lasting 13C polarization (T1 = 3.7 ± 0.25 and 1.7 ± 0.1 min) is demonstrated for the C1 and C2 nuclear sites, respectively. The remarkable polarization levels become possible as a result of favorable relaxation dynamics at the microtesla fields. The ultralong polarization lifetimes will be conducive to yielding high polarization after purification, quality assurance, and injection of the hyperpolarized molecular imaging probes. These results pave the way to future in vivo translation of carbon-13 hyperpolarized molecular imaging probes prepared by this approach.

13C Radiofrequency Amplification by Stimulated Emission of Radiation Threshold Sensing of Chemical Reactions.

Conventional nuclear magnetic resonance (NMR) enables detection of chemicals and their transformations by exciting nuclear spin ensembles with a radio-frequency pulse followed by detection of the precessing spins at their characteristic frequencies. The detected frequencies report on chemical reactions in real time and the signal amplitudes scale with concentrations of products and reactants. Here, we employ Radiofrequency Amplification by Stimulated Emission of Radiation (RASER), a quantum phenomenon producing coherent emission of 13C signals, to detect chemical transformations. The 13C signals are emitted by the negatively hyperpolarized biomolecules without external radio frequency pulses and without any background signal from other, nonhyperpolarized spins in the ensemble. Here, we studied the hydrolysis of hyperpolarized ethyl-[1-13C]acetate to hyperpolarized [1-13C]acetate, which was analyzed as a model system by conventional NMR and 13C RASER. The chemical transformation of 13C RASER-active species leads to complete and abrupt disappearance of reactant signals and delayed, abrupt reappearance of a frequency-shifted RASER signal without destroying 13C polarization. The experimentally observed "quantum" RASER threshold is supported by simulations.

Diagnosis and treatment of MPN in real life: exploratory and retrospective chart review including 960 MPN patients diagnosed with ET or MF in Germany.

PURPOSE: The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification. METHODS: In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022. Physicians reported available data obtained from patient charts via paper-pencil based survey (secondary use of data). Patient features were evaluated using descriptive analysis, also including diagnostic assessment, therapeutic strategies and risk stratification. RESULTS: Data of 960 MPN patients diagnosed with essential thrombocythemia (ET) (n = 495) or myelofibrosis (MF) (n = 465) after implementation of the revised 2016 WHO classification of myeloid neoplasms was collected from the patient charts. While they met at least one minor WHO-criteria for primary myelofibrosis, 39.8% of those diagnosed with ET did not have histological BM testing at diagnosis. 63.4% of patients who were classified as having MF, however, did not obtain an early prognostic risk assessment. More than 50% of MF patients showed characteristics consistent with the pre-fibrotic phase, which was emphasized by the frequent use of cytoreductive therapy. Hydroxyurea was the most frequently used cytoreductive medication in 84.7% of ET and 53.1% of MF patients. While both ET and MF cohorts showed cardiovascular risk factors in more than 2/3 of the cases, the use of platelet inhibitors or anticoagulants varied between 56.8% in ET and 38.1% in MF patients. CONCLUSIONS: Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria.

Thoracoscopic Resection of Lung Nodules following CT-Guided Labeling in Children and Adolescents with Solid Tumors.

Resection of lung metastases in children with solid tumors is regularly hampered by limited intraoperative detectability and relevant operative trauma of the open surgical access. The aim of this study was to analyze thoracoscopic resection of lung metastases in children following CT-guided labeling with coil wires. We retrospectively analyzed data of children and adolescents undergoing this approach at our institution between 2010 and 2022 with regard to technical aspects as well as surgical and oncological data. Within this period, we performed this procedure on 12 patients wherein we resected 18 lesions (1-5 per patient). The median age of patients was 178 months (51-265). The median duration of coil wire placement was 41 min (30-173) and the median surgery time was 53 min (11-157). No conversions were necessary and no intraoperative complications occurred. Complete microscopic resection (R0) was achieved in all labeled lesions and malignant tumor components were found in 5/12 patients. Our study shows that with a careful patient selection, thoracoscopic resection of lung metastases after coil wire labeling is a safe and reproducible procedure in children. Using this approach, lesions that are expected to have a reduced intraoperative detectability during open surgery become resectable. Patients benefit from the minimally invasive surgical access and reduced operative trauma.

The significance of margins in pediatric Non-Rhabdomyosarcoma soft tissue sarcomas: Consensus on surgical margin definition harmonization from the INternational Soft Tissue SaRcoma ConsorTium (INSTRuCT).

BACKGROUND: Margin status following surgery in children, adolescents, and young adults with soft tissue sarcomas is controversial and has been defined differently by various specialties, with definitions changing over time and by cooperative group. The International Soft Tissue Sarcoma Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, European pediatric Soft Tissue sarcoma Study Group (EpSSG), and the European Cooperative Weichteilsarkom Studiengruppe (CWS) devoted to improving patient outcomes by pooling and mining cooperative group clinical trial data. METHODS: The INSTRuCT non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) working group aimed to develop international harmonized recommendations regarding surgical margin assessment and definitions in children and adolescents with soft tissue tumors. RESULTS AND CONCLUSION: This review addresses accepted principles and areas of controversy, including the perspectives of surgeons, pathologists, radiation oncologists, and pediatric oncologists, to develop a framework for building common guidelines for future research.

Developments in the Surgical Approach to Staging and Resection of Rhabdomyosarcoma.

Although survival after rhabdosarcoma treatment has improved over the years, one third of patients still develop locoregional relapse. This review aims to highlight developments pertaining to staging and local treatment of specific RMS tumor sites, including head and neck, chest/trunk, bladder-prostate, female genito-urinary, perianal, and extremity sites.

Two-cavities approach for resection of pediatric abdominal neuroblastic tumors: experience of a national reference pediatric onco-surgical center.

PURPOSE: Surgery of complex neuroblastic tumors often requires additional procedures, especially in the situation of tumor extension within thorax and impossibility of securing the aorta above the tumor. These situations prompt the opening of the thoracic cavity. The concern regarding increased operative trauma and morbidity associated with this approach make surgeons reluctant regarding this technique. The aim of this study was to evaluate the efficacy of two-cavities approach based on our experience in a reference pediatric onco-surgical center. METHODS: Between 2003 and 2021, we operated on 232 neuroblastic tumors. 31/232 patients with complex, advanced-stage neuroblastic tumors underwent tumor resection through a two-cavities approach. A retrospective review of patient's records was performed. RESULTS: The median age at operation was 48 months (5-180). 23/31 patients presented image-defined risk factors (IDRF). The approach most commonly used was the transverse laparotomy with incision of the diaphragm (n = 14), followed by the thoraco-abdominal incision (n = 10). Gross total resection (GTR) was achieved in 24 patients, a near-GTR in 4 cases, and an incomplete resection in 3 cases. Median duration of surgery was 288 min (99-900) and median duration of mechanical ventilation was 22 h (0-336). Postoperative complications occurred in 10 patients, 6/10 required surgical reintervention. The 5-year overall survival (OS) was 90% and the 5-year event-free survival (EFS) was 50%. CONCLUSIONS: The two-cavities approach for resection of abdominal neuroblastoma in children is a safe technique with no added morbidity.

Parahydrogen-Induced Carbon-13 Radiofrequency Amplification by Stimulated Emission of Radiation.

The feasibility of Carbon-13 Radiofrequency (RF) Amplification by Stimulated Emission of Radiation (C-13 RASER) is demonstrated on a bolus of liquid hyperpolarized ethyl [1-13 C]acetate. Hyperpolarized ethyl [1-13 C]acetate was prepared via pairwise addition of parahydrogen to vinyl [1-13 C]acetate and polarization transfer from nascent parahydrogen-derived protons to the carbon-13 nucleus via magnetic field cycling yielding C-13 nuclear spin polarization of approximately 6 %. RASER signals were detected from samples with concentration ranging from 0.12 to 1 M concentration using a non-cryogenic 1.4T NMR spectrometer equipped with a radio-frequency detection coil with a quality factor (Q) of 32 without any modifications. C-13 RASER signals were observed for several minutes on a single bolus of hyperpolarized substrate to achieve 21 mHz NMR linewidths. The feasibility of creating long-lasting C-13 RASER on biomolecular carriers opens a wide range of new opportunities for the rapidly expanding field of C-13 magnetic resonance hyperpolarization.

Evaluation of functional and metabolic tumor volume using voxel-wise analysis in childhood rhabdomyosarcoma.

BACKGROUND: Cross-sectional imaging-based morphological characteristics of pediatric rhabdomyosarcoma have failed to predict outcomes. OBJECTIVE: To evaluate the feasibility and possible value of generating tumor sub-volumes using voxel-wise analysis of metabolic and functional data from positron emission tomography/magnetic resonance imaging (PET/MR) or PET/computed tomography (CT) and MRI in rhabdomyosarcoma. MATERIALS AND METHODS: Thirty-four examinations in 17 patients who received PET/MRI or PET/CT plus MRI were analyzed. The volume of interest included total tumor volume before and after therapy. Apparent diffusion coefficients (ADC) and standard uptake values (SUV) were determined voxel-wise. Voxels were assigned to three different groups based on ADC and SUV: "viable tumor tissue," "intermediate tissue" or "possible necrosis." In a second approach, data were grouped into three clusters using the Gaussian mixture model. The ratio of these clusters to total tumor volume and changes due to chemotherapy were correlated with clinical and histopathological data. RESULTS: After chemotherapy, the proportion of voxels in the different groups changed significantly. A significant reduction of the proportion of voxels assigned to cluster 1 was found, from a mean of 36.4% to 2.5% (P < 0.001). There was a significant increase in the proportion of voxels in cluster 3 following chemotherapy from 24.8% to 81.6% (P = 0.02). The proportion of voxels in cluster 2 differed depending on the presence or absence of tumor recurrence, falling from 48% to 10% post-chemotherapy in the group with no tumor recurrence (P < 0.05) and from 29% to 23% (P > 0.05) in the group with tumor recurrence. CONCLUSION: Voxel-wise evaluation of multimodal data in rhabdomyosarcoma is feasible. Our initial results suggest that the different distribution of sub-volumes before and after therapy may have prognostic significance.

Metabolic Tumor Imaging with Rapidly Signal-Enhanced 1-13 C-Pyruvate-d3.

The metabolism of malignant cells differs significantly from that of healthy cells and thus, it is possible to perform metabolic imaging to reveal not only the exact location of a tumor, but also intratumoral areas of high metabolic activity. Herein, we demonstrate the feasibility of metabolic tumor imaging using signal-enhanced 1-13 C-pyruvate-d3 , which is rapidly enhanced via para-hydrogen, and thus, the signal is amplified by several orders of magnitudes in less than a minute. Using as a model, human melanoma xenografts injected with signal-enhanced 1-13 C-pyruvate-d3, we show that the conversion of pyruvate into lactate can be monitored along with its kinetics, which could pave the way for rapidly detecting and monitoring changes in tumor metabolism.

Detailed functional results after bladder-preserving surgery and high-dose-rate brachytherapy in pediatric bladder/prostate rhabdomyosarcoma.

PURPOSE: In pediatric bladder/prostate-rhabdomyosarcoma, the rate of bladder preservation after neoadjuvant chemotherapy is high, with an excellent oncological outcome. Information about functional urological long-term outcomes is rare. METHODS: Data of all patients who had undergone bladder-preserving surgery with or without brachytherapy at our institution between 2009 and 2020 were analyzed retrospectively. Detailed urological function was assessed focusing on age-related continence, bladder capacity and urodynamic findings. RESULTS: We identified 40 patients, median age at surgery of 27 months (range 9-191), and 32 patients additionally received postoperative high-dose-rate brachytherapy. The median follow-up was 32.5 months (range 6-125). The bladder capacity increased from median 66.7% (21.1-180) of expected bladder capacity related to age 3 months after surgery to 87.4% (58.1-181.8) 9 months after surgery. In the group of aged > 6-year-old, continence was 94% (83% with brachytherapy, 100% without brachytherapy). Erectile function was normal in 92% (90% with brachytherapy, 100% without brachytherapy). Bladder capacity was more than 65% expected bladder capacity related to age in 70% (60% with brachytherapy, 86% without brachytherapy). 65% of all patients need neither anticholinergic drugs nor low-dose antibiotics (63% with brachytherapy, 71% without brachytherapy). CONCLUSIONS: Bladder preservation with good functional outcome can be achieved in localized bladder/prostate-rhabdomyosarcoma. In selected cases, supportive brachytherapy additionally contributes to an improvement in the oncological outcome with calculable risks for bladder and erectile function. Careful urological aftercare should be a fixed priority after oncological follow-ups.

Quantification of Prostate Cancer Metabolism Using 3D Multiecho bSSFP and Hyperpolarized [1-13 C] Pyruvate: Metabolism Differs Between Tumors of the Same Gleason Grade.

BACKGROUND: Three-dimensional (3D) multiecho balanced steady-state free precession (ME-bSSFP) has previously been demonstrated in preclinical hyperpolarized (HP) 13 C-MRI in vivo experiments, and it may be suitable for clinical metabolic imaging of prostate cancer (PCa). PURPOSE: To validate a signal simulation framework for the use of sequence parameter optimization. To demonstrate the feasibility of ME-bSSFP for HP 13 C-MRI in patients. To evaluate the metabolism in PCa measured by ME-bSSFP. STUDY TYPE: Retrospective single-center cohort study. PHANTOMS/POPULATION: Phantoms containing aqueous solutions of [1-13 C] lactate (2.3 M) and [13 C] urea (8 M). Eight patients (mean age 67 ± 6 years) with biopsy-confirmed Gleason 3 + 4 (n = 7) and 4 + 3 (n = 1) PCa. FIELD STRENGTH/SEQUENCES: 1 H MRI at 3 T with T2 -weighted turbo spin-echo sequence used for spatial localization and spoiled dual gradient-echo sequence used for B0 -field measurement. ME-bSSFP sequence for 13 C MR spectroscopic imaging with retrospective multipoint IDEAL metabolite separation. ASSESSMENT: The primary endpoint was the analysis of pyruvate-to-lactate conversion in PCa and healthy prostate regions of interest (ROIs) using model-free area under the curve (AUC) ratios and a one-directional kinetic model (kP ). The secondary objectives were to investigate the correlation between simulated and experimental ME-bSSFP metabolite signals for HP 13 C-MRI parameter optimization. STATISTICAL TESTS: Pearson correlation coefficients with 95% confidence intervals and paired t-tests. The level of statistical significance was set at P < 0.05. RESULTS: Strong correlations between simulated and empirical ME-bSSFP signals were found (r > 0.96). Therefore, the simulation framework was used for sequence optimization. Whole prostate metabolic HP 13 C-MRI, observing the conversion of pyruvate into lactate, with a temporal resolution of 6 seconds was demonstrated using ME-bSSFP. Both assessed metrics resulted in significant differences between PCa (mean ± SD) (AUC = 0.33 ± 012, kP  = 0.038 ± 0.014) and healthy (AUC = 0.15 ± 0.10, kP  = 0.011 ± 0.007) ROIs. DATA CONCLUSION: Metabolic HP 13 C-MRI in the prostate using ME-bSSFP allows for differentiation between aggressive PCa and healthy tissue. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.