IgG4 porta-hepatis pseudotumor mimicking a hilar cholangiocarcinoma.

A 60-year-old female with a BRCA2 mutation and a history of breast cancer presented with diffuse abdominal pain and elevated liver enzymes. Imaging revealed a porta-hepatis mass, prompting consideration of hilar cholangiocarcinoma or breast cancer metastasis. Further investigation including biopsy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography findings were inconsistent with malignancy, leading to investigation of non-neoplastic causes. Elevated IgG4 levels suggested IgG4-related disease, a mass-forming fibroinflammatory condition. This case demonstrates IgG4-related disease exclusively impacting the portal vein and underscores the importance of considering IgG4-related disease in the differential diagnosis of hepatic masses.

EUS-guided versus percutaneous liver biopsy: A prospective randomized clinical trial.

Background and Objectives: Prospective studies comparing EUS-guided liver biopsy (EUS-LB) to percutaneous LB (PC-LB) are scarce. We compared the efficacy and safety of EUS-LB with those of PC-LB in a prospective randomized clinical trial. Methods: Between 2020 and 2021, patients were enrolled and randomized (1:1 ratio). The primary outcome was defined as the proportion of patients with ≥11 complete portal tracts (CPTs). The sample size (n = 80) was calculated based on the assumption that 60% of those in the EUS-LB and 90% of those in the PC-LB group will have LB with ≥11 CPTs. The secondary outcomes included proportion of patients in whom a diagnosis was established, number of CPTs, pain severity (Numeric Rating Scale-Pain Intensity), duration of hospital stay, and adverse events. Results: Eighty patients were enrolled (median age, 53 years); 67.5% were female. Sixty percent of those in the EUS-LB and 75.0% of those in the PC-LB group met the primary outcome (P = 0.232). The median number of CPTs was higher in the PC-LB (17 vs 13; P = 0.031). The proportion of patients in whom a diagnosis was established was similar between the groups (92.5% [EUS-LB] vs 95.0% [PC-LB]; P = 1.0). Patients in the EUS-LB group had less pain severity (median Numeric Rating Scale-Pain Intensity, 2.0 vs 3.0; P = 0.003) and shorter hospital stay (2.0 vs 4.0 hours; P < 0.0001) compared with the PC-LB group. No patient experienced a serious adverse event. Conclusions: EUS-guided liver biopsy was safe, effective, better tolerated, and associated with a shorter hospital stay.

Urinoma formation following renal mass cryoablation treated with nephroureteral stent placement.

Renal cryoablation (CA) has become an accepted treatment option for patients with small renal tumors and co-morbidities that make them less favorable for surgical intervention. Complications from renal CA have been previously reported and are generally associated with increasing size and central location of the tumor. Ureteral injury from renal CA, although rare, can be difficult to manage and may require complex surgeries in patients who are poor surgical candidates to begin with. We report a case of a renal mass CA complicated by proximal ureteral necrosis and transection, treated with multiple minimally invasive procedures ultimately resulting in successful bridging of the necrotic segment with nephroureteral stent and thus avoiding major surgery.

Noninvasive and Highly Multiplexed Five-Color Tumor Imaging of Multicore Near-Infrared Resonant Surface-Enhanced Raman Nanoparticles In Vivo.

In vivo multiplexed imaging aims for noninvasive monitoring of tumors with multiple channels without excision of the tissue. While most of the preclinical imaging has provided a number of multiplexing channels up to three, Raman imaging with surface-enhanced Raman scattering (SERS) nanoparticles was suggested to offer higher multiplexing capability originating from their narrow spectral width. However, in vivo multiplexed SERS imaging is still in its infancy for multichannel visualization of tumors, which require both sufficient multiplicity and high sensitivity concurrently. Here we create multispectral palettes of gold multicore-near-infrared (NIR) resonant Raman dyes-silica shell SERS (NIR-SERRS) nanoparticle oligomers and demonstrate noninvasive and five-plex SERS imaging of the nanoparticle accumulation in tumors of living mice. We perform the five-plex ratiometric imaging of tumors by varying the administered ratio of the nanoparticles, which simulates the detection of multiple biomarkers with different expression levels in the tumor environment. Furthermore, since this method does not require the excision of tumor tissues at the imaging condition, we perform noninvasive and longitudinal imaging of the five-color nanoparticles in the tumors, which is not feasible with current ex vivo multiplexed tissue analysis platforms. Our work surpasses the multiplicity limit of previous preclinical tumor imaging methods while keeping enough sensitivity for tumor-targeted in vivo imaging and could enable the noninvasive assessment of multiple biological targets within the tumor microenvironment in living subjects.

Image-guided percutaneous cryo-ablation of peri-urethral unresectable recurrent pelvic malignancy: A case report and brief review.

Recurrent or metastatic peri-urethral pelvic malignancies are a difficult-to-treat entity. Re-resection is recommended when possible but is frequently unfavorable due to scar tissue, fibrosis, and obliteration of tissue planes following previous interventions such as surgical resection and/or radiation therapy. Curative options for patients that have unresectable cancer are limited. Cryo-ablation has been extensively studied in the treatment of unresectable renal, liver and lung malignancies and has the potential to provide definitive treatment for recurrent pelvic malignancy. There is a paucity of reports of salvage cryo-ablation in patients with recurrent pelvic malignancies, as most of these tumors are located close to critical structures that could be irreversibly injured by thermal ablation and are hence treated with some form of radiation therapy. But, for patients who fail surgical and radiation treatments, options are limited. Here, we describe two cases of regional tumor recurrence in the pelvis treated with percutaneous cryoablation using protective techniques to avoid thermal injury to adjacent structures. In each case, cryo-ablation was performed successfully despite extensive previous surgical and radiation interventions. Salvage cryo-ablation resulted in a positive clinical and imaging response with an improvement in quality of life and absence of recurrence on follow-up imaging which continues to persist at the writing of this manuscript about 8 and 12-months following treatment.

The Pain Crisis: Interventional Radiology's Role in Pain Management.

Pain is a complex syndrome that is difficult to treat. The increasing numbers of patients living with chronic diseases has led to increasing pain management needs and the rise of opioid use disorder (OUD) as a major and potentially lethal public health concern. Treatment of chronic pain with prescription opioids alone is not always successful, and a multidisciplinary approach is paramount to address the needs of patients at risk of developing or suffering from OUD. Interventional radiologists trained to perform minimally invasive procedures with negligible downtime and postprocedure pain can help stem the tide of opioid-related deaths and disability. This article reviews a wide range of minimally invasive procedures, including vertebral augmentation, sacroplasty, thermal ablation of osseous metastasis, nerve blocks, and gonadal vein embolization, that interventional radiologists are now using successfully to treat chronic pain. The evidence to support use of such procedures is highlighted. This article also briefly discusses emerging techniques such as arterial embolization and ablation for knee and shoulder osteoarthritis that have not yet been fully tested but exhibit strong potential in chronic pain management. By reducing opioid use in patients suffering from chronic pain, these minimally invasive procedures can potentially prevent escalation to OUD.

Risk Factors for Major Hemorrhage Following Percutaneous Image-Guided Renal Biopsy: What is the "core" of the Problem? A Retrospective Case-control Study.

OBJECTIVES: Percutaneous renal biopsy (PRB) plays a critical role in the work-up of renal parenchymal disease. Although it is considered a low-risk procedure, additional interventions may be required in about 7% of the cases following biopsy. The purpose of this study was to identify risk factors for major hemorrhage by microscopic analysis of the cores obtained following PRB, with an intent to enhance the sensitivity and specificity of the risk stratification process, especially in patients undergoing this procedure in an outpatient setting. MATERIAL AND METHODS: A retrospective review identified 17 of 179 patients (9.50%) with major hemorrhage following PRB between July 2014 and June 2019. Using propensity score matching, 26 controls (without major hemorrhage) were matched to 17 cases (with major hemorrhage). The biopsy cores obtained from the cases and controls were analyzed by a single pathologist for medullary, cortical, total (medullary + cortical) lengths, and the number of arcuate arteries (AAs). Medullary:cortical (M:C), cortical:total (C:T), and medullary:total (M:T) length ratios were then calculated. RESULTS: A stratified version of logistic regression was used to test for an association between each of the variables identified on the cores and the probability of a major hemorrhage. The analysis revealed that there was a statistically significant association between the number of AAs per specimen with the risk of major hemorrhage (P = 0.0006). When 0, 1, or >2 AAs were identified, the frequency of major hemorrhage was 13.04%, 66.67%, and 75.00%, respectively. The odds of major hemorrhage were 6 times higher with one AA and (95% CI, 1.28-32.30) and 15 times higher with >2 AAs (95% CI, 1.41-169.57). No significant association was found between medullary length (P = 0.228), medulla:cortex (M:C) (P = 0.089), medulla:total (M:T) (P = 0.108), or cortex:total (C:T) (P = 0.112) length ratios and major hemorrhage. CONCLUSION: There was a strong and incremental correlation between major renal hemorrhage following PRB and the number of AAs per core specimen. Identification of AAs by the pathologist, while assessing for sample adequacy, in the US suite can help predict major hemorrhage in patients undergoing PRBs.

Chemorefractory liver metastasis from cervical cancer successfully treated with a combination of yttrium-90 and immunotherapy.

Liver metastases in cervical cancer is rare and can be difficult-to-treat. The current guidelines established by the Gynecologic Oncology Group recommend platinum-based systemic chemotherapy in combination with an anti-angiogenic agent such as bevacizumab, however, overall survival remains poor following diagnosis and options for patients who fail chemotherapy are limited. Yttrium-90 (Y90) radioembolization (RE) has shown great promise in the treatment of chemo-refractory colorectal liver metastases. We describe a 30-year-old female with a history of stage IB endocervical adenocarcinoma who later developed metastases to the liver, that were unresponsive to multiple chemotherapeutics and chemoembolization, and was successfully treated with Y90 RE with concurrent systemic Pembrolizumab. The Y90 RE treatment resulted in positive clinical and imaging responses with improvement in her quality of life, all of which continue to persist at the time of writing this manuscript about 8-months into her RE treatment.

Role of Computed Tomography-guided Biopsies in the Era of Electromagnetic Navigational Bronchoscopy: A Retrospective Study of Factors Predicting Diagnostic Yield in Electromagnetic Navigational Bronchoscopy and Computed Tomography Biopsies.

OBJECTIVES: Over 25% of the high-risk population screened for lung cancer have an abnormal computed tomography (CT) scan. Conventionally, these lesions have been biopsied with CT guidance with a high diagnostic yield. Electromagnetic navigational bronchoscopy (ENB) with transbronchial biopsy has emerged as a technology that improves the diagnostic sensitivity of conventional bronchoscopic biopsy. It has been used to biopsy lung lesions, due to the low risk of pneumothorax. It is, however, a new technology that is expensive and its role in the diagnosis of the solitary pulmonary nodule (SPN) is yet to be determined. The purpose of this study was to evaluate the diagnostic yield of CT-guided biopsy (CTB) following non-diagnostic ENB biopsy and identify characteristics of the lesion that predicts a low diagnostic yield with ENB, to ensure appropriate use of ENB in the evaluation of SPN. MATERIALS AND METHODS: One hundred and thirty-five lung lesions were biopsied with ENB from January 2017 to August 2019. Biopsies were considered diagnostic if pathology confirmed malignancy or inflammation in the appropriate clinical and imaging setting. We evaluated lesions for several characteristics including size, lobe, and central/peripheral distribution. The diagnostic yield of CTB in patients who failed ENB biopsies was also evaluated. Logistic regression was used to identify factors likely to predict a non-diagnostic ENB biopsy. RESULT: Overall, ENB biopsies were performed in 135 patients with solitary lung lesions. ENB biopsies were diagnostic in 52% (70/135) of the patients. In 23 patients with solitary lung lesions, CTBs were performed following a non-diagnostic ENB biopsy. The CTBs were diagnostic in 87% of the patients (20/23). ENB biopsies of lesions <21.5 mm were non-diagnostic in 71% of cases (42/59); 14 of these patients with non-diagnostic ENB biopsies had CTBs, and 86% of them were diagnostic (12/14). ENB biopsies of lesions in the lower lobes were non- diagnostic in 59% of cases (35/59); 12 of these patients with non-diagnostic ENB biopsies had CTBs, and 83% were diagnostic (10/12). ENB biopsies of lesions in the outer 2/3 were non-diagnostic in 57% of cases (50/87); 21 of these patients with non-diagnostic ENB biopsies had CTBs, and 86% were diagnostic (18/21). CONCLUSION: CTBs have a high diagnostic yield even following non-diagnostic ENB biopsies. Lesions <21.5 mm, in the outer 2/3 of the lung, and in the lower lung have the lowest likelihood of a diagnostic yield with ENB biopsies. Although CTBs have a slightly higher pneumothorax rate, these lesions would be more successfully diagnosed with CTB as opposed to ENB biopsy, in the process expediting the diagnosis and saving valuable medical resources.

Metastatic retro-crural lymph nodes from transitional cell carcinoma of bladder successfully treated with single session cryoablation.

Bladder cancer (BC) is a relatively common tumor, with a male preponderance. High-grade muscle invasive bladder cancer (MIBC) has a very high incidence of pelvic lymph node metastasis at presentation. Involvement of the retro-crural lymph nodes, although has been described in other pelvic tumors, is very uncommon for BC. Cryoablation in the retro-crural region is extremely challenging due to the proximity to the critical structures like inferior venacava and aorta and has not been extensively reported. We describe a 56-year old male patient with MIBC who underwent extensive treatments including radical cystoprostatectomy, chemoradiation and immunotherapy, ultimately with localized disease in the retro-crural region. Single session cryoablation of these lymph nodes was performed with a curative intent yielding a positive response that has persisted for more than 2 years.

Metastatic appendiceal cancer treated with Yttrium 90 radioembolization and systemic chemotherapy: A case report.

BACKGROUND: Primary appendiceal cancers are rare, and they generally present with liver and/or peritoneal metastases. Currently there are no guidelines to treat metastatic appendiceal cancer, and hence they are treated as metastatic colorectal cancer. Combining Yttrium 90 (Y-90) radioembolization (RE) with systemic chemotherapy early in the treatment of right sided colon cancers has been shown to improve survival. Based on this data, a combination of systemic chemotherapy and Y-90 RE was used to treat a case of metastatic appendiceal cancer. CASE SUMMARY: A 76-year-old male presented to the emergency room with progressive right lower quadrant pain. A Computed Tomography of the abdomen and pelvis was performed which showed acute appendicitis and contained perforation. Urgent laparoscopic appendectomy was then followed by histological analysis, which was significant for appendiceal adenocarcinoma. After complete workup he underwent right hemicolectomy and lymph node dissection. He received adjuvant chemotherapy as the local lymph nodes were positive. Follow-up imaging was significant for liver metastasis. Due to rapid growth of the liver lesions and new peritoneal nodules, the patient was treated with a combination of Y-90 RE and folinic acid, fluorouracil, and irinotecan with bevacizumab and not microwave ablation as previously planned. Follow up imaging demonstrated complete response of the liver lesions. At 12-mo follow-up, the patient continued to enjoy good quality of life with no recurrent disease. CONCLUSION: Utilization of Y-90 RE concomitantly with systemic chemotherapy early in the treatment of appendiceal cancer may provide improved control of this otherwise aggressive cancer.

Nanomedicine for Spontaneous Brain Tumors: A Companion Clinical Trial.

Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS). We used gold nanoparticles due to their surface plasmon effect that enables their sensitive and microscopic resolution detection using the SERS technique. Raman microscopy of the resected tumors showed heterogeneous EPR of nanoparticles into oligodendrogliomas and meningiomas of different grades, without any detectable traces in necrotic parts of the tumors or normal brain. Raman observations were confirmed by scanning electron microscopy (SEM) and X-ray elemental analyses, which enabled localization of individual nanoparticles embedded in tumor tissues. Our results demonstrate nanoparticles' EPR and its variations in clinically relevant, spontaneous brain tumors. Such heterogeneities should be considered alongside routine preoperative imaging and histopathological analyses in order to accelerate clinical management of brain tumors using nanomedicine approaches.

Detection of Premalignant Gastrointestinal Lesions Using Surface-Enhanced Resonance Raman Scattering-Nanoparticle Endoscopy.

Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of precancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, premalignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types.

Bis(dialkylphosphino)ferrocene-Ligated Nickel(II) Precatalysts for Suzuki-Miyaura Reactions of Aryl Carbonates.

Aryl carbonates, a common protecting group in synthetic organic chemistry, are potentially valuable electrophiles in cross-coupling reactions. Here, after performing a thorough evaluation of different precatalysts, we demonstrate that (dcypf)Ni(2-ethylphenyl)(Br) (dcypf = 1,1-bis-(dicyclohexylphosphino)ferrocene) is an efficient precatalyst for Suzuki-Miyaura reactions using a variety of aryl carbonates as substrates. Mechanistic studies indicate that (dcypf)Ni(2-ethylphenyl)(Br), which contains a bidentate phosphine that binds in a trans geometry, is an effective precatalyst for these reactions for two reasons: (i) it rapidly forms the Ni(O) active species and (ii) it minimizes comproportionation reactions between the Ni(O) active species and both the unactivated Ni(II) precatalyst and on-cycle Ni(II) complexes to form catalytically inactive Ni(I) species. In contrast, the state of the art precatalyst (dppf)Ni(o-tolyl)(Cl) (dppf = 1,1-bis(diphenylphosphino)ferrocene), which contains a bidentate phosphine that binds in a cis geometry, forms Ni(I) species during activation and is essentially inactive for aryl carbonate couplings. Although the exact reasons on a molecular level why the dcypf system is more active than the dppf system are unclear, our results indicate that in general Ni catalysts supported by the dcypf ligand will give better performance for catalytic reactions involving substrates which undergo relatively slow oxidative addition, such as aryl carbonates.

A Raman Imaging Approach Using CD47 Antibody-Labeled SERS Nanoparticles for Identifying Breast Cancer and Its Potential to Guide Surgical Resection.

Raman spectroscopic imaging has shown great promise for improved cancer detection and localization with the use of tumor targeting surface enhanced Raman scattering (SERS) nanoparticles. With the ultrasensitive detection and multiplexing capabilities that SERS imaging has to offer, scientists have been investigating several clinical applications that could benefit from this unique imaging strategy. Recently, there has been a push to develop new image-guidance tools for surgical resection to help surgeons sensitively and specifically identify tumor margins in real time. We hypothesized that SERS nanoparticles (NPs) topically applied to breast cancer resection margins have the potential to provide real-time feedback on the presence of residual cancer in the resection margins during lumpectomy. Here, we explore the ability of SERS nanoparticles conjugated with a cluster of differentiation-47 (CD47) antibody to target breast cancer. CD47 is a cell surface receptor that has recently been shown to be overexpressed on several solid tumor types. The binding potential of our CD47-labeled SERS nanoparticles was assessed using fluorescence assisted cell sorting (FACS) on seven different human breast cancer cell lines, some of which were triple negative (negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2)). Xenograft mouse models were also used to assess the ability of our Raman imaging system to identify tumor from normal tissue. A ratiometric imaging strategy was used to quantify specific vs. nonspecific probe binding, resulting in improved tumor-to-background ratios. FACS analysis showed that CD47-labeled SERS nanoparticles bound to seven different breast cancer cell lines at levels 12-fold to 70-fold higher than isotype control-labeled nanoparticles (p < 0.01), suggesting that our CD47-targeted nanoparticles actively bind to CD47 on breast cancer cells. In a mouse xenograft model of human breast cancer, topical application of CD47-targeted nanoparticles to excised normal and cancer tissue revealed increased binding of CD47-targeted nanoparticles on tumor relative to normal adjacent tissue. The findings of this study support further investigation and suggest that SERS nanoparticles topically applied to breast cancer could guide more complete surgical resection during lumpectomy.

Surface-Enhanced Raman Scattering Nanoparticles for Multiplexed Imaging of Bladder Cancer Tissue Permeability and Molecular Phenotype.

Bladder cancer has the highest recurrence rate of all cancers due in part to inadequate transurethral resection. Inadequate resection is caused by the inability of cystoscopes to detect invisible lesions during the resection procedure. To improve detection and resection of nonmuscle invasive bladder cancer, we quantified the ability of a surface-enhanced Raman nanoparticle and endoscope system to classify bladder tissue as normal or cancerous. Both antibody-based (active) and tissue permeability-based (passive) targeting mechanisms were evaluated by topically applying nanoparticles to ex vivo human bladder tissue samples. Multiplexed molecular imaging of CD47 and Carbonic Anhydrase 9 tumor proteins gave a receiver operating characteristic area under the curve (ROC AUC of 0.93 (0.75, 1.00). Furthermore, passively targeted nanoparticles enabled tissue classification with an ROC AUC of 0.93 (0.73, 1.00). Passively targeted nanoparticles penetrated 5-fold deeper and bound to tumor tissue at 3.3-fold higher concentrations in cancer compared to normal bladder urothelium, suggesting the existence of an enhanced surface permeability and retention effect in human bladder cancer.

Multi-spin echo spatial encoding provides three-fold improvement of temperature precision during intermolecular zero quantum thermometry.

PURPOSE: Intermolecular multiple quantum coherences (iMQCs) are a source of MR contrast with applications including temperature imaging, anisotropy mapping, and brown fat imaging. Because all applications are limited by signal-to-noise ratio (SNR), we developed a pulse sequence that detects intermolecular zero quantum coherences with improved SNR. METHODS: A previously developed pulse sequence that detects iMQCs, HOMOGENIZED with off resonance transfer (HOT), was modified with a multi-spin echo spatial encoding scheme (MSE-HOT). MSE-HOT uses a series of refocusing pulses to generate a stack of images that are averaged in postprocessing for higher SNR. MSE-HOT performance was quantified by measuring its temperature accuracy and precision during hyperthermia of ex vivo red bone marrow samples. RESULTS: MSE-HOT yielded a three-fold improvement in temperature precision relative to previous pulse sequences. Sources of improved precision were 1) echo averaging and 2) suppression of J-coupling in the methylene protons of fat. MSE-HOT measured temperature change with an accuracy of 0.6°C. CONCLUSION: MSE-HOT improved the temperature accuracy and precision of HOT to a level that is sufficient for hyperthermia of bone marrow.

Intermolecular zero quantum coherences enable accurate temperature imaging in red bone marrow.

PURPOSE: Red bone marrow metastases are common in breast and prostate cancer patients, but those metastases are currently incurable. Recent developments show that hyperthermia could be a successful treatment for bone metastasis, but thermometry remains difficult or inaccurate in red marrow. METHOD: The technique evaluated in this study measures the evolution frequency of intermolecular zero quantum coherences (iZQCs) between fat and water. The iZQC evolution frequency was mapped linearly to temperature. The temperature accuracy and coherence lifetime of the iZQC method were evaluated against other thermometry methods that are based on localized spectroscopy and multiple gradient echo imaging. RESULTS: The temperature coefficient (α) was 9.8 ± 0.7 ppb/°C with the iZQC method and 2 ± 7 ppb/°C with traditional localized spectroscopy. CONCLUSION: Because the accuracy of thermometry is limited by the reproducibility of α between samples, iZQCs provide nearly a 10-fold accuracy improvement in red marrow (0.7 ppb/°C for iZQCs versus 7 ppb/°C for localized spectroscopy.) The iZQC technique in this study will for the first time allow accurate and quantitative thermal imaging of red marrow. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. Magn Reson Med 74:63-70, 2015. © 2014 Wiley Periodicals, Inc.

A method to convert MRI images of temperature change into images of absolute temperature in solid tumours.

PURPOSE: During hyperthermia (HT), the therapeutic response of tumours varies substantially within the target temperature range (39-43 °C). Current thermometry methods are either invasive or measure only temperature change, which limits the ability to study tissue responses to HT. This study combines manganese-containing low temperature sensitive liposomes (Mn-LTSL) with proton resonance frequency shift (PRFS) thermometry to measure absolute temperature in tumours with high spatial and temporal resolution using MRI. METHODS: Liposomes were loaded with 300 mM MnSO(4). The phase transition temperature (T(m)) of Mn-LTSL samples was measured by differential scanning calorimetry (DSC). The release of manganese from Mn-LTSL in saline was characterised with inductively coupled plasma atomic emission spectroscopy. A 2T GE small animal scanner was used to acquire dynamic T1-weighted images and temperature change images of Mn-LTSL in saline phantoms and fibrosarcoma-bearing Fisher-344 rats receiving hyperthermia after Mn-LTSL injection. RESULTS: The T(m) of Mn-LTSL in rat blood was 42.9 ± 0.2 °C (DSC). For Mn-LTSL samples (0.06 mM-0.5 mM Mn(2+) in saline) heated monotonically from 30 °C to 50 °C, a peak in the rate of MRI signal enhancement occurred at 43.1° ± 0.3 °C. The same peak in signal enhancement rate was observed during heating of fibrosarcoma tumours (N = 3) after injection of Mn-LTSL, and the peak was used to convert temperature change images into absolute temperature. Accuracies of calibrated temperature measurements were in the range 0.9-1.8 °C. CONCLUSION: The release of Mn(2+) from Mn-LTSL affects the rate of MR signal enhancement which enables conversion of MRI-based temperature change images to absolute temperature.