Magnetic Resonance Imaging Response Research Articles

Ultrasmall Fe3O4 nanoparticles self-assembly induced dual-mode T1/T2-weighted magnetic resonance imaging and enhanced tumor synergetic theranostics

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.

Disentangling the intrinsic relaxivities of highly purified graphene oxide

The chemistry of contrast agents (CAs) for magnetic resonance imaging (MRI) applications is an active area of research and, in recent work, it was shown that CA-based graphene oxide (GO) has valuable properties for biomedical uses. GO has a potential as MRI CAs thanks to several functionalities, like its ability to penetrate tissues and cell membranes, as well as easy coupling with therapeutic agents, therefore showing the potential for both a diagnostic and therapeutic role. In this study, we performed a thorough cleaning of the GO sample (synthesized using a modified Hummers method), minimizing the amount of residual manganese down to 73 ppm. Using a wide range of physical–chemical methods (morphology, chemical composition, elemental analysis, spectroscopies, and imaging), we characterized the intrinsic longitudinal and transverse relaxivities of highly purified GO nanosheets. X-band electron paramagnetic resonance allowed to recognize the paramagnetic species involved, and 1.0 T MRI was used to disentangle the relative contributions to the MRI contrast of pristine GO nanosheets arising from structural defects and residual paramagnetic manganese impurities embedded in the nanomaterial. Although experiments show that the MRI relaxivity of GO nanosheets arises from the cumulative effect of structural defects and paramagnetic impurities, we conclude that the latter contribution to the longitudinal and transverse relaxivities becomes irrelevant for highly purified (pristine) GO. This novel finding clearly demonstrates that, apart from trivial manganese inclusion, pristine GO produces an inherent MRI response via structural defects, and therefore it is on its own a suitable candidate as MRI contrast agent.

Findings in magnetic resonance imaging for restaging locally advanced rectal cancer

PurposeWe aimed to assess the prognostic value of restaging magnetic resonance imaging (MRI) in rectal cancer after neoadjuvant therapy and compare long-course chemoradiotherapy (LC-CRT) to short-course radiotherapy with delayed surgery (SCRT-delay).MethodsThis retrospective study included 267 patients with locally advanced rectal cancer (LARC) operated on between January 2016 and April 2019, all of whom received either LC-CRT or SCRT-delay in the neoadjuvant setting. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS) based on radiological response assessed using the magnetic resonance tumor regression grade (mrTRG).ResultsIn the LC-CRT group, cumulative 1-, 3-, and 5-year OS rates were 94.8%, 86.4%, and 79.0%, while in the SCRT-delay group, they were 83.3%, 68.9%, and 68.9% (P = 0.017). For CSS in the LC-CRT group, cumulative rates were 96.9%, 90.3%, and 85.0%, and in the SCRT-delay group, they were 88.6%, 81.4%, and 81.4% (P = 0.222). There were no significant differences in total histological response rates or local recurrence rates between the treatment groups. The good and moderate response group (mrTRG 1–3) had significantly better cumulative 1-, 3-, and 5-year OS and CSS compared to the poorer response group (mrTRG 4–5) (P = 0.023 for OS and P = 0.048 for CSS).ConclusionUnfavorable MRI response is a sign of poor prognosis in LARC. SCRT-delay is comparable to LC-CRT concerning the oncological outcome.

Gd3+ Complexes for MRI Detection of Zn2+ in the Presence of Human Serum Albumin: Structure-Activity Relationships.

Zn2+-responsive magnetic resonance imaging (MRI) contrast agents are typically composed of a Gd chelate conjugated to a Zn2+-binding moiety via a linker. They allow for Zn2+ detection in the presence of human serum albumin (HSA). In order to decipher the key parameters that drive their Zn2+-dependent MRI response, we designed a pyridine-based ligand, PyAmC2mDPA, and compared the properties of GdPyAmC2mDPA to those of analogue complexes with varying Gd core, Zn-binding moiety, or linker sizes. The stability constants determined by pH potentiometry showed the good selectivity of PyAmC2mDPA for Gd3+ (log KGd = 16.27) versus Zn2+ (log KZn = 13.58), proving that our modified Zn2+-binding DPA moiety prevents the formation of previously observed dimeric species. Paramagnetic relaxation enhancement measurements indicated at least three sites that are available for GdPyAmC2mDPA binding on HSA, as well as a 2-fold affinity increase when Zn2+ is present (KD = 170 μM versus KDZn = 60 μM). Fluorescence competition experiments provided evidence of the higher affinity for site II vs site I, as well as the importance of both the Zn-binding part and the Gd core in generating enhanced HSA affinity in the presence of Zn2+. Finally, an analysis of nuclear magnetic relaxation dispersion (NMRD) data suggested a significantly increased rigidity for the Zn2+-bound system, which is responsible for the Zn2+-dependent relaxivity response.

Association between Tumor Volume Change on MRI with Surgical Margin Status, Pathological Response, and Local Control Following Pre-Operative Radiation Therapy for Soft Tissue Sarcoma

The clinical significance of radiographic progression during pre-operative radiation therapy (RT) for soft tissue sarcoma (STS) remains unclear. We sought to evaluate associations between radiographic change on T1 post-contrast (T1c) and T2 weighted magnetic resonance imaging (MRI) with percent pathological response (PR%), positive surgical margins (+SM), and local control (LC). We retrospectively identified patients with STS undergoing neoadjuvant RT who had both pre- and post-RT MRI prior to surgical resection. Gross tumor volumes were contoured on pre- and post-RT T1c and T2 MRI sequences and relative change in volume from baseline was calculated. Radiographic classification was defined as response (>30% reduction), progression (>30% increase), or stable (≤30% reduction or ≤30% increase). Chi squared, Fishers Exact, and Kruskal Wallis (KW) tests were used to assess differences between groups. Linear and binary logistic regression models used to assess associations between MRI response and PR% and +SM, respectively. LC was modeled with Kaplan Meier methods and log rank tests. A total of 68 STS patients were identified, with a median follow up of 49 months (range 7-229). With a median age of 60.5 years (25-88) and tumor size of 10.8cm (2.7-25.7), the most common histologies were undifferentiated pleomorphic sarcoma (UPS; 32.4%) and myxoid liposarcoma (ML; 16.2%), and were primarily grade 2-3 disease (89.7%). With a median RT dose of 50 Gy in 25 fractions (44-60Gy), the median radiographic volume change was 2% (-86.4 to 953.6%) and -2.1% (-89.6 to 962.5%) for T1c and T2, respectively. Radiographic classification of response/stable/progression was 25.4%/49.2%/25.4% and 27.9%/52.5%/19.7% for T1c and T2, respectively. Histology (ML vs. UPS) and grade (1 vs. 3) were predictors for radiographic response on both T1c (72.7% vs 18.8%, p = 0.03 and 71.4% vs. 10.4%, p = 0.03) and T2 (71.5% vs. 18.2%, p = 0.02 and 71.4% vs. 14.6%, p = 0.002), respectively. With 6 +SM (8.8%), the rate of +SM for response/stable/progression was 20%/10.3%/0% in T1c (p = 0.2) and 5.9%/12.5%/0% in T2 (p = 0.5). As a continuous variable, neither relative change on T1c (p = 0.2) or T2 (p = 0.4) were associated with +SM. With an overall median PR% of 64% (0-100%), the median PR% was significantly different for response/stable/progression for both T1c (95%/42%/73%, p = 0.02) and T2 (95%/50%/87.5%, p = 0.04). Radiographic change on neither T1c (p = 0.4) or T2 (p = 0.5) were associated with PR% on a continuous basis. With a total of 4 local recurrences, there was no significant difference in LC by radiographic classification on either T1c (p = 0.65) or T2 (p = 0.85). While radiographic response may be correlated with pathological response, radiographic progression on either T1c or T2 following neoadjuvant RT was not associated with a detriment in surgical margins or local control. These findings suggest that STS radiographic "pseudoprogression" is not associated with worse outcome.

Association of biophysics-based biomarker with tumor volumetric response in breast cancer treated with immunotherapy.

608 Background: The treatment landscape of triple negative breast cancer (TNBC) has rapidly changed in recent years, with immuno-oncology (IO) therapies, such as immune checkpoint inhibitors, leading to improvement in patient outcomes. However, the number of patients who benefit is less than 15%, and the therapy itself can prompt severe immune-related adverse events. Breast cancer tumor volume measurements derived from magnetic resonance imaging (MRI) have proven to be a strong predictor of outcome (survival) in patients who either achieve pathological complete response (pCR) or have residual cancer burden (RCB) (ACRIN6657/CALGB150007 I-SPY1). Using an integrative computational approach, we developed both the TumorIO biomarker and the TumorIO Score to predict response to IO therapy in breast cancer patients. Here, we assess the volumetric response in IO-treated patients and its relationship with the TumorIO Score. Methods: We assessed the relationship between breast tumor volumetric response to IO therapy and the TumorIO Score, a previously developed metric that relates probability of IO responsiveness to spatially-resolved tumor biology. We grouped patients into TumorIO Score high vs. low populations, and compared final volumes assessed by MRI and percent response to therapy between groups. Results: We analyzed the volumetric response of IO-treated patients from the I-SPY2 trial and from an independent cohort (total n = 67). Over 96% of the IO-treated patients in the I-SPY2 trial (n = 55) had a greater than 90% volumetric response, while in the independent cohort (n = 12) only 50% of patients had greater than 90% volumetric response. Across both cohorts, 95.8% of patients with a high TumorIO Score achieved > 90% reduction in tumor volume. Additionally, we identified three patients in our cohort that appeared not to respond to IO therapy, who were later classified as progressor, pseudo-progressor, and non-responder patients. The TumorIO biomarker was able to differentiate these three patients, as it associates a unique distinctive biological phenomenon with either response or lack of response. Conclusions: The TumorIO Score provides a novel technology to address several challenges in neoadjuvant IO therapy, namely: predicting which patients are likely to have pCR in response to IO therapy, as well as identifying patients likely to have a substantial volumetric response to IO. Additionally, this method may facilitate subcategorizing patients likely to show radiological pseudo-progression prior to IO administration, although a larger cohort is needed to validate these findings.

Abstract P4-07-40: Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy

Abstract Background Radiological complete response (CR-MRI) to neoadjuvant chemotherapy (NAC) by MRI predicts pathologic complete response (pCR) rates in pts with TNBC treated preoperatively with A/TX-based regimens and in some studies, it correlates with disease-free survival (DFS). The main aim of this study was to assess the relevance of the MRI response to primary chemotherapy associated with clinical stage and HER2 expression (Zero vs Low), in a cohort of 143 TNBC pts treated with A and TX +/- carboplatin (CP) in the NAC setting. Methods Retrospective study of pts treated with NAC for TNBC between January 2002 and June 2021, who underwent MRI to assess tumour response before NAC, after 4 cycles of anthracycline and cyclophosphamide (AC) and after TX. Survival analysis was based on the Kaplan-Meier and survival curves were compared using the log-rank test. A p value of less than 0.05 was considered as statistically significant. Results A total of 143 TNBC pts with a median age of 52 years; 7, 63 and 73 pts had stage I, II and III disease, respectively. The NAC regimen consisted in 117 pts 4 cycles of AC followed by TX and in 24 pts the same adding CP (in 21 pts with non-CR-MRI, 2 with CR-MRI and 1 without MRI after AC). PCR was observed in 41%. Of 30 pts with CR-MRI after AC, 83% obtain a pCR (p< 0.001), and of 52 pts with CR-MRI at the end of NAC, 70.7% obtain a pCR (p< 0,001) of which 90% had a CR-MRI after AC. Adding CP increased pCR by 6% (p=0.564). According HER2-zero vs low expression, the pCR was 38% and 47% respectively, with no significant differences. With a median follow-up of 60 months, 34% recurred and 16% died of TNBC. In pts with pCR, the DFS at 5 years (y) was 96% and 47% for pts without pCR (p< 0.001), with a DFS of 91% if CR-MRI at the end of NAC and 48% if non-CR-MRI (p< 0.001). In HER2-Zero tumours the DFS at 5 y was 64% vs 66% in HER-2 low. Interestingly, overall survival (OS) at 5 y was 72% in HER2-Zero and 84% in HER2-low (p=0.080). Conclusions Performing serial MRI in the course of NAC in TNBC may be a reliable indicator of pCR, adding platinum to TX in pts with CR-MRI may increase pCR rate. HER2-Zero expression in TNBC, seems to confer worse OS rates. Citation Format: Marina Sierra Boada, Luis Antonio Fernandez, Elsa Dalmau, Gemma Llort, Maria Marin, Pablo Andreu, Natalia Lopez, Carla Climent, Marta Rodriguez, Sandra Soriano, Miquel Angel Segui. Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-40.

MRI to assess response after neoadjuvant chemotherapy in breast cancer subtypes: a systematic review and meta-analysis

This meta-analysis aimed to estimate and compare sensitivity, specificity, positive- (PPV) and negative predictive value (NPV) of magnetic resonance imaging (MRI) for predicting pathological complete remission (pCR) after neoadjuvant chemotherapy (NAC) in patients with early-stage breast cancer. We stratified for molecular subtype by immunohistochemistry (IHC) and explored the impact of other factors. Two researchers systematically searched PUBMED and EMBASE to select relevant studies and extract data. For meta-analysis of sensitivity and specificity, we used bivariate random-effects models. Twenty-six included studies contained 4497 patients. There was a significant impact of IHC subtype on post-NAC MRI accuracy (p = 0.0082) for pCR. The pooled sensitivity was 0.67 [95% CI 0.58–0.74] for the HR−/HER2−, 0.65 [95% CI 0.56–0.73] for the HR−/HER2+, 0.55 [95% CI 0.45–0.64] for the HR+/HER2− and 0.60 [95% CI 0.50–0.70] for the HR+/HER2+ subtype. The pooled specificity was 0.85 [95% CI 0.81–0.88] for the HR−/HER2−, 0.81 [95% CI 0.74–0.86] for the HR−/HER2+, 0.88[95% CI 0.84–0.91] for the HR+/HER2− and 0.74 [95% CI 0.63–0.83] for the HR+/HER2+ subtype. The PPV was highest in the HR-/HER2- subtype and lowest in the HR+/HER2− subtype. MRI field strength of 3.0 T was associated with a higher sensitivity compared to 1.5 T (p = 0.00063). The accuracy of MRI for predicting pCR depends on molecular subtype, which should be taken into account in clinical practice. Higher MRI field strength positively impacts accuracy. When intervention trials based on MRI response evaluation are designed, the impact of IHC subtype and field strength on MR accuracy should be considered.

A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods

BackgroundObesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity. MethodsWe report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18–45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to <35, 35 to <40, ≥40 kg/m2). We investigate the efficacy, safety, and mechanisms of oxytocin administration in reducing body weight. Secondary endpoints include changes in resting energy expenditure, body composition, caloric intake, metabolic profile, and brain activation via functional magnetic resonance imaging in response to food images and during an impulse control task. Safety and tolerability (e.g., review of adverse events, vital signs, electrocardiogram, comprehensive metabolic panel) are assessed throughout the study and six weeks after treatment completion. ResultsSixty-one male and female participants aged 18–45 years were randomized (mean age 34 years, mean BMI 37 kg/m2). The study sample is diverse with 38% identifying as non-White and 20% Hispanic. ConclusionInvestigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae.

A Prospective Study of Magnetic Resonance Imaging-guided Focal Salvage High-dose-Rate Brachytherapy for Radiorecurrent Prostate Cancer: Updated Results of 30 Patients

PurposeLimited prospective data on focal salvage high-dose-rate (HDR) prostate brachytherapy is available. We sought to explore the toxicities, health-related quality of life (HRQoL), and efficacy of focal salvage HDR brachytherapy in a prospective clinical trial. This report presents the updated results of previously published data. Methods and MaterialsPatients with locally recurrent prostate cancer after previous external beam radiation therapy and/or brachytherapy were enrolled. Patients received magnetic resonance imaging (MRI)-guided, ultrasound-based focal HDR brachytherapy delivered over 2 fractions of 13.5 Gy delivered 1 to 2 weeks apart. Androgen deprivation therapy (ADT) was not used. ResultsThirty patients were treated between 2012 and 2019. At a median follow-up time of 39 months, the 3-year biochemical failure-free rate was 61.8% (95% confidence interval, 44.0%-86.6%), and the 3-year ADT/salvage therapy-free rate was 86.0% (95% confidence interval, 74.1%-99.8%). Seventeen patients experienced subsequent biochemical failure, 9 received ADT and/or further local salvage, and no patients died of prostate cancer. Of the 28 patients who had posttreatment MRI, 26 had a local treatment response. No acute grade ≥3 genitourinary/gastrointestinal toxicity was observed. One temporary late grade 3 genitourinary toxicity event occurred, but no late grade ≥3 gastrointestinal toxicity was seen. No significant decline in urinary or bowel HRQoL was observed. ConclusionsFocal salvage HDR brachytherapy has a favorable side effect profile, no significant decline in HRQoL, and the 3-year biochemical control rates are in line with those of other salvage options. Early MRI response at the treated site is common, but does not preclude subsequent biochemical failure.

Combined PET-CT and MRI for response evaluation in patients with squamous cell anal carcinoma treated with curative-intent chemoradiotherapy

ObjectivesTo assess the effectiveness of fluorine-18 fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) for response assessment post curative-intent chemoradiotherapy (CRT) in anal squamous cell carcinoma (ASCC).MethodsConsecutive ASCC patients treated with curative-intent CRT at a single centre between January 2018 and April 2020 were retrospectively identified. Clinical meta-data including progression-free survival (PFS) and overall survival (OS) outcomes were collated. Three radiologists evaluated PET-CT and MRI using qualitative response assessment criteria and agreed in consensus. Two-proportion z test was used to compare diagnostic performance metrics (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy). Kaplan-Meier analysis (Mantel-Cox log-rank) was performed.ResultsMRI (accuracy 76%, PPV 44.8%, NPV 95.7%) and PET-CT (accuracy 69.3%, PPV 36.7%, NPV 91.1%) performance metrics were similar; when combined, there were statistically significant improvements (accuracy 94.7%, PPV 78.9%, NPV 100%). Kaplan-Meier analysis demonstrated significant differences in PFS between responders and non-responders at PET-CT (p = 0.007), MRI (p = 0.005), and consensus evaluation (p < 0.001). Cox regression analysis of PFS demonstrated a lower hazard ratio (HR) and narrower 95% confidence intervals for consensus findings (HR = 0.093, p < 0.001). Seventy-five patients, of which 52 (69.3%) were females, with median follow-up of 17.8 months (range 5–32.6) were included. Fifteen of the 75 (20%) had persistent anorectal and/or nodal disease after CRT. Three patients died, median time to death 6.2 months (range 5–18.3).ConclusionCombined PET-CT and MRI response assessment post-CRT better predicts subsequent outcome than either modality alone. This could have valuable clinical benefits by guiding personalised risk-adapted patient follow-up.Key Points• MRI and PET-CT performance metrics for assessing response following chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC) were similar.• Combined MRI and PET-CT treatment response assessment 3 months after CRT in patients with ASCC was demonstrated to be superior to either modality alone.• A combined MRI and PET-CT assessment 3 months after CRT in patients with ASCC has the potential to improve accuracy and guide optimal patient management with a greater ability to predict outcome than either modality alone

P-265 Neoadjuvant radiotherapy for locally advanced rectal cancer during the first wave of COVID19 pandemic: Guy’s cancer cohort experience

The Covid-19 pandemic is a healthcare emergency with a significant impact on cancer services provision. In March 2020, our institution adopted the ESMO expert consensus guidelines for radiotherapy management of rectal cancer during the pandemic. Here we present short-term oncological outcomes of this approach compared to the same period in 2018. Patients who underwent neoadjuvant (chemo) radiotherapy for rectal cancer between 1st March 2020 and 31 May 2020 were identified from a research ethics committee (REC)-approved research database for cancer patients (Guy’s Cancer Cohort). Patient demographics and treatment characteristics were extracted and compared with a control cohort treated in the same period in 2018. The definition of local response was based on identification of downstaging on re-staging Magnetic Resonance Imaging (MRI) post neoadjuvant treatment (mrT3c/d-4 to mrT0-2 and mrT2 to mrT0-1) and classified in a binary format (response vs no response). In addition, in patients who underwent total mesorectal excision (TME), neoadjuvant rectal (NAR) score was calculated, as described previously, and classified into low (<8), intermediate (>=8<=16) and high (>16). The frequency of MRI and pathological response was compared using non-parametric Fisher exact test. Thirty patients were treated in the three-month period in 2020 as compared with 21 in 2018 (43% increase). No statistically significant differences were observed in baseline tumour characteristics. The use of neoadjuvant short-course radiotherapy (SCRT) treatment increased significantly from 19% of cases in 2018 to 50% during the pandemic, which was reflected in reduced radiotherapy-related hospital footfall (median 15 appointments in 2020 vs 25 appointments in 2018). While the use of concomitant fluoropyrimidines was lower (47 vs 71%), the use of induction chemotherapy was higher (30 vs 19%) in 2020 compared to 2018, which may reflect more prevalent use of total neoadjuvant treatment. There was no difference in the proportion of MRI responders between cohorts (52% in 2020 vs 38% in 2018). In patients who underwent TME, there was no difference in the proportion of R1 resection (0 in 2020 vs 9% in 2018), median NAR scores (8 (1-30) in 2020 v 15 (range 4-50) in 2018) or NAR score categories (22% good responders, 64% intermediate and 14% non-responders during Covid-19 vs 9% good responders, 55% intermediate and 36% non-responders in 2018). Changes in radiotherapy treatment of rectal cancer during Covid-19 pandemic, including more frequent use of SCRT (often in combination with neoadjuvant chemotherapy), did not seem to have negatively impacted short-term oncological outcomes, as measured by MRI downstaging rates and NAR scores following TME. The effect of the pandemic on medium and long-term oncological outcomes is still awaited.

Prognostic value of response evaluation based on breast MRI after neoadjuvant treatment: a retrospective cohort study.

To investigate the impact of response evaluation after neoadjuvant chemotherapy (NAC) in breast cancer patients, assessed by both magnetic resonance imaging (MRI) and pathology, on disease-free survival (DFS). This single-center, retrospective cohort study included consecutive breast cancer patients who underwent NAC and preoperative breast MRI. Resolution of invasive carcinoma in the breast and axilla was defined as complete pathological response (pCR). Radiological complete response (rCR) was defined as the absence of abnormal enhancement in the tumor site. Kaplan-Meier estimator was used to estimate the disease-free survival on 60 months. Cox regression analysis was used to estimate hazard ratio (HR) values. In total, 317 patients were included with a mean age of 47.3 years and a mean tumor size of 39.8 mm. The most common immunophenotype was luminal (44.9%), followed by triple-negative (26.8%). Overall, 126 patients (39.7%) had an rCR, while 119 (37.5%) had pCR; the radiological and pathological responses agreed in 252 cases (79.5%). During follow-up, patients who had rCR and pCR had a better DFS curve compared to patients with non-rCR and non-pCR, while those who had rCR or pCR presented an intermediate curve (Log-rank p = 0.003). Multivariate analysis showed a higher risk of recurrence in patients with non-rCR and non-pCR (HR: 5,626; p = 0.020) and those who had a complete response on MRI or pathology only (HR: 4,369; p = 0.067), when compared to patients with rCR and pCR. The association of MRI and pathological responses after NAC might better stratify the risk of recurrence and prognosis in breast cancer patients. • Association of response evaluation after neoadjuvant chemotherapy by pathology and MRI allows better stratification of prognosis. • Complete response to neoadjuvant chemotherapy on pathology and MRI was related to better disease-free survival. • Complete response on MRI or pathology only had a greater risk of recurrence.

Breast-Conserving Therapy in Patients with cT3 Breast Cancer with Good Response to Neoadjuvant Systemic Therapy Results in Excellent Local Control: A Comprehensive Cancer Center Experience.

Many cT3 breast cancer patients are treated with mastectomy, regardless of response to neoadjuvant systemic therapy (NST). We evaluated local control of cT3 patients undergoing breast-conserving therapy (BCT) based on magnetic resonance imaging (MRI) evaluation post-NST. In addition, we analyzed predictive characteristics for positive margins after breast-conserving surgery (BCS). All cT3 breast cancer patients who underwent BCS after NST between 2002 and 2015 at the Netherlands Cancer Institute were included. Local recurrence-free interval (LRFI) was estimated using the Kaplan-Meier method, and predictors for positive margins were analyzed using univariable analysis and multivariable logistic regression. Of 114 patients undergoing BCS post-NST, 75 had negative margins, 16 had focally positive margins, and 23 had positive margins. Of those with (focally) positive margins, 12 underwent radiotherapy, 6 underwent re-excision, and 21 underwent mastectomy. Finally, 93/114 patients were treated with BCT (82%), with an LRFI of 95.9% (95% confidence interval [CI] 91.5-100%) after a median follow-up of 7 years. Predictors for positive margins in univariable analysis were hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) subtype, lobular carcinoma, and non-mass enhancement (NME) on pre-NST MRI. MRI response was not correlated to positive margins. In multivariable regression, the odds of positive margins were decreased in patients with HER2-positive (HER2+; odds ratio [OR] 0.27, 95% CI 0.10-0.73; p=0.01) and TN tumors (OR 0.17, 95% CI 0.03-0.82; p=0.028). A trend toward positive margins was observed in patients with NME (OR 2.38, 95% CI 0.98-5.77; p=0.055). BCT could be performed in 82% of cT3 patients in whom BCT appeared feasible on post-NST MRI. Local control in these patients was excellent. In those patients with HR+/HER2- tumors, NME on MRI, or invasive lobular carcinoma, the risk of positive margins should be considered preoperatively.

Myocardial changes on 3T cardiovascular magnetic resonance imaging in response to haemodialysis with fluid removal

BackgroundMapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping.MethodsThis is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2.ResultsTwenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (− 25 ml, p = 0.002), LV stroke volume (− 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (− 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters.ConclusionsAcute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.

Gamma Knife Thalamotomy for a Medically Refractory Tremors: Longitudinal Evaluation of Clinical Effects and MRI Response Patterns.

The present longitudinal study evaluated the results of Gamma Knife surgery (GKS) for medically refractory tremors. The outcome after Gamma Knife thalamotomy targeting the ventral intermediate nucleus (VIM) was analyzed in 17 patients (9 men and 8 women; mean age 72years) with either Parkinson's disease or an essential tremor, who were followed up for at least 2years after treatment. Clinical and magnetic resonance imaging (MRI) examinations were done before and every 3months after GKS. The mean rates of symptom improvement (a decrease in the tremor frequency) were 6%, 39%, 63%, and 64% at 3, 6, 12, and 24monthsafter treatment, respectively. The defined MRI response patterns included a minimum reaction (in 3 patients), a normal reaction (in 11 patients), and a hyperreaction (in 3 patients). They were not associated with any evaluated pretreatment, radiosurgical, or outcome parameter, although 2 patients with a hyperreaction exhibited mild-to-moderate motor weakness in the contralateral limbs. Linear contrasting of the border between the thalamus and the internal capsule adjacent to the lesion site was noted on follow-up MRI in 13 cases and was associated with a higher symptom improvement rate. GKS allows effective and safe management of medically refractory tremors. The treatment is characterized by variable MRI response patterns. Some imaging findings during follow-up may be associated with clinical effects.

The Effects of Kisspeptin on Brain Response to Food Images and Psychometric Parameters of Appetite in Healthy Men.

The hormone kisspeptin has crucial and well-characterized roles in reproduction. Emerging data from animal models also suggest that kisspeptin has important metabolic effects including modulation of food intake. However, to date there have been no studies exploring the effects of kisspeptin on brain responses to food stimuli in humans. This work aims to investigate the effects of kisspeptin administration on brain responses to visual food stimuli and psychometric parameters of appetite, in healthy men. A double-blinded, randomized, placebo-controlled, crossover study was conducted. Participants included 27 healthy, right-handed, eugonadal men (mean ± SEM: age 26.5 ± 1.1 years; body mass index 23.9 ± 0.4 kg/m2). Participants received an intravenous infusion of 1 nmol/kg/h of kisspeptin or rate-matched vehicle over 75 minutes. Measurements included change in brain activity on functional magnetic resonance imaging in response to visual food stimuli and change in psychometric parameters of appetite, during kisspeptin administration compared to vehicle. Kisspeptin administration at a bioactive dose did not affect brain responses to visual food stimuli or psychometric parameters of appetite compared to vehicle. This is the first study in humans investigating the effects of kisspeptin on brain regions regulating appetite and demonstrates that peripheral administration of kisspeptin does not alter brain responses to visual food stimuli or psychometric parameters of appetite in healthy men. These data provide key translational insights to further our understanding of the interaction between reproduction and metabolism.

Effect of Structure and Intramolecular Distances on Photoswitchable Magnetic Resonance Imaging Contrast Agents.

Light-activated sensors are of great interest for biological applications but are limited by the depth of penetration of light. We have been interested in transducing light activation to a magnetic signal that can be detected through noninvasive imaging by magnetic resonance imaging (MRI). We have previously developed agents incorporating spiropyran derivatives as the sensing moiety and characterized features that influence photoswitching; however, we found the MRI response to be unpredictable. In this work, we delve deeper into the potential mechanisms for the observed MRI responses in an effort to better understand the structural effects on controlling magnetic properties. A series of light-activatable MRI contrast agents were synthesized and characterized to assess the effect of spiropyran positioning on contrast agent functions and properties. These compounds are based on the same spiropyran skeleton, also named 1',3',3'-trimethyl-6-nitrospiro[chromene-2,2-indoline], which is linked with an MRI contrast agent, gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (DO3A). We investigated the photo-to-magnetic conversion properties of these novel compounds by adjusting linker lengths over a range from three to seven methylene groups. The primary results indicated that the contrast agent with a five-carbon linker (25) showed the highest light-sensing ability after irradiation with visible light. The results will aid in the design of future spiropyran-based MRI sensors.

Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma

Background and purposeOxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma. Materials and methodsT2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8–10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy. A mean T1 was extracted from manually segmented tumour regions of interest and a paired two-tailed t-test was used to compare changes across the patient population. Regions of subcutaneous fat and muscle tissue were examined as control ROIs. ResultsThere was a significant increase in T1 of the tumour ROIs across patients following the 8–10 fractions of chemoradiotherapy (paired t-test, p < 0.001, n = 7). At baseline, prior to receiving chemoradiotherapy, there were no significant changes in T1 across patients from breathing oxygen (n = 9). In the post-chemoRT scans (8–10 fractions), there was a significant decrease in T1 of the tumour ROIs across patients when breathing 100% oxygen (paired t-test, p < 0.001, n = 8). Out of the 12 patients from which we successfully acquired a visit 1 T1-map, only 1 patient did not respond to treatment, therefore, we cannot correlate these results with clinical outcome. ConclusionsThese clinical data demonstrate feasibility and potential for T1-mapping and oxygen enhanced T1-mapping to indicate perfusion or treatment response in tumours of this nature. These data show promise for future work with a larger cohort containing more non-responders, which would allow us to relate these measurements to clinical outcome.

Correlations Between Vestibular Function and Imaging of the Semicircular Canals in DFNA9 Patients.

Background and Purpose: Radiologic abnormalities on computed tomography (CT), including narrowing or sclerosis of the semicircular canals (SCCs), and T2-weighted magnetic resonance imaging (MRI), including signal loss in the SCC, have been reported as potential biomarkers in patients with P51S mutations in the COCH gene (i.e., DFNA9). The aim of our study was to correlate caloric responses through electronystagmography (ENG) data with imaging results in DFNA9 patients.Materials and Methods: A retrospective study was performed in 45 patients; therefore, 90 ears with P51S mutations in the COCH gene were tested. Caloric responses and CT and MRI data were analyzed from June 2003 until May 2014. More than half of patients (54%) were candidates for cochlear implantation.Results: In our population, 91% of tested ears had sclerotic lesions and/or narrowing in one or more SCCs on CT scan. All tested ears had narrowing or signal loss in at least one SCC on T2-weighted MRI. The lateral SCC was affected in 87% on CT scan and 92% on MRI. However, in 83% of tested ears, all three SCCs were affected on MRI. Furthermore, in 77% of tested ears, caloric responses were reduced bilaterally, while 11.5% showed unilateral hypofunction and the other 11.5% had normal caloric responses. CT abnormalities correlated with hypofunction of caloric responses. This statistically significant difference was present if abnormalities were observed in at least one of the SCCs as well as in ipsilateral lateral SCC function loss. MRI abnormalities in at least one of the SCCs correlated with ENG hypofunction, but there was no direct correlation between lateral SCC abnormalities on MRI and caloric responses of the investigated lateral canal.Conclusion: Our retrospective analysis confirms the presence of CT and MRI abnormalities in DFNA9 patients with the P51S mutation in the COCH gene. A correlation between these radiologic features and vestibular function (tested by means of caloric response) was found in this population.