Serial MRI Scans Research Articles

Prospective longitudinal analysis of imaging-based spatiotemporal tumor habitats in glioblastoma, IDH-wild type: implication in patient outcome using multiparametric physiologic MRI

BackgroundPhysiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT).MethodsIn this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats.DiscussionThe perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma.Trial registrationClinicalTrials.gov ID: NCT02613988.

Clinical and radiological effects of Bevacizumab for the treatment of radionecrosis after stereotactic brain radiotherapy

PurposeThe purpose of this multicenter retrospective study was to analyze the clinical and radiological effects of bevacizumab (BV) on radionecrosis (RN) that developed after stereotactic radiotherapy (SRT) for brain metastasis.MethodsForty patients with SRT related symptomatic brain RN treated in 10 radiation oncology centers were analyzed. The clinical response to BV treatment was categorized as follows: complete (no additional treatment required), partial (requiring either steroids or repeat BV), and unresponsive (requiring surgery). The radiological features of brain RN were analyzed in 10 patients whose serial MRI scans were available after corticosteroid and BV treatments.ResultsBV was used as a first line treatment in 11 (27.5%) and as a second line treatment in 29 (72.5%) of patients. The neurological symptoms regressed in 77.5% of patients after treatment with BV (45% complete response, 32.5% partial response). The median edema volume increased from 75.9 cc (range: 5.9-125.8 cc) at RN to 113.65 cc (range: 1.5-382.1 cc) after use of corticosteroids, representing a rate of 39.8% increase (p = 0.074). However, after BV treatment the median volume of edema decreased to 19.5 cc (range: 0-163.3 cc) which represents a difference of 62.2% (p = 0.041) from RN.ConclusionThe use of BV caused clinical response rate of 77.5% and a good radiological response in corticosteroid unresponsive patients. The role of BV should be further investigated in prospective studies.

Abstract PO1-28-07: Neoadjuvant docetaxel plus cisplatin versus docetaxel plus doxorubicin and cyclophosphamide in early-stage triple-negative breast cancer (HNBC-001): results from a multicenter, randomized controlled, open-label phase II trial

Abstract Background: Adding platinum to anthracycline- and taxane-based neoadjuvant chemotherapy has improved pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC). However, the efficacy of combining docetaxel and platinum without anthracycline remains controversial. Methods: The HNBC-001 trial was a randomized, phase 2 controlled, and open-label investigation carried out in China at 6 hospitals. The participants who were aged 18–70 years, were histologically confirmed for TNBC clinical stage II–III, suitable for potentially curative surgery, and had an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 were selected for this trial. Participants were randomly categorized into two equal groups; those who received docetaxel plus cisplatin (75 mg/m2, respectively) and those who received docetaxel plus doxorubicin and cyclophosphamide (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2). These regimens were given every 3 weeks for 6 cycles. Randomization was stratified by tumor size and nodal status. The primary endpoint was the number of individuals achieving a pCR (ypT0/is ypN0). The trial was registered with chictr.org (number ChiCTR-1800019501). Results: Between November 28, 2018, and June 11, 2022, 212 patients were selected (n=106/treatment). The number of individuals who achieved pCR after docetaxel plus cisplatin treatment was 51.9%, and that of those who attained pCR after docetaxel plus doxorubicin and cyclophosphamide was 35.8% (P=0.019). After 21 months of median follow-up [interquartile range (IQR), 13 to 33], 11 of 106 patients (10.4%) in the docetaxel plus cisplatin group and 14 of 106 patients (13.2%) in the docetaxel plus doxorubicin and cyclophosphamide group had event-free survival (EFS) events [95% confidence interval (CI) =0.360 to 1.783, hazard ratio (HR) =0.801, P=0.585]. The incidence of grade 3 or 4 events was similar in both groups [57 (54%) vs. 51 (48%)]. However, no treatment-associated deaths were identified. Conclusions: In stage II to III TNBC, the docetaxel plus cisplatin regimen achieved higher pCR rates than docetaxel plus doxorubicin and cyclophosphamide, with a manageable toxicity profile. Consistent with the literature, the docetaxel plus cisplatin regimen demonstrated a favorable risk-to-benefit profile and could serve as an optimal neoadjuvant chemotherapy option for patients with high-risk TNBC. table 1: Patient characteristics figure 1: Study endpoints Error bars denote 95% CIs based on normal approximation. p values were calculated from the Chi-square test. (A) Frequency of patients who achieved a pathological complete response per treatment group (primary endpoint). (B) Frequency of patients who achieved a clinical breast tumour response per treatment group, assessed by serial MRI scans after completion of neoadjuvant treatment. (C) Frequency of patients who achieved a minimal residual disease (residual cancer burden class 0 or 1). (D) Frequency of patients who received breast-conservation surgery. table 2: Treatment-emergent adverse events Citation Format: Dechuang Jiao, Jianghua Qiao, Chengzheng Wang, Juntao Li, Xianfu Sun, Zhenduo Lu, Chongjian Zhang, Lianfang Li, Min Yan, Yueqing Feng, Yong Zhou, Miao Deng, Xinlan Liu, Mingde Ma, Haiquan Jia, Qingxin Xia, Xiuchun Chen, Zhenzhen Liu. Neoadjuvant docetaxel plus cisplatin versus docetaxel plus doxorubicin and cyclophosphamide in early-stage triple-negative breast cancer (HNBC-001): results from a multicenter, randomized controlled, open-label phase II trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-28-07.

Mechanisms underlying the laxative effect of lactulose: A randomized placebo-controlled trial showing increased small bowel water and motility unaltered by the 5-HT3 receptor antagonist, ondansetron.

Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti-diarrheal actions of ondansetron. A double-blind, randomized, placebo-controlled crossover study of the effect of ondansetron 8 mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6 h after a meal. Participants then received lactulose 13.6 g twice daily and study drug for a further 36 h. On Day 3, they had further serial MRI scans for 4 h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content. Lactulose increased area under the curve (AUC) of SBWC from 0 to 240 min, mean difference 14.2 L · min (95% CI 4.1, 24.3), p = 0.009, and substantially increased small bowel motility after 4 h (mean (95% CI) 523 (457-646) a.u. to 852 (771-1178) a.u., p = 0.007). There were no changes in T1AC after 36 h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose. Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti-diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.

PATH-53. ANAPLASTIC PLEOMORPHIC XANTHROASTROCYTOMA WITH BEND5-NTRK2 FUSION IN A YOUNG ADULT WITH A HISTORY OF CRANIAL RADIATION FOR CHILDHOOD RHABDOMYOSARCOMA

Abstract INTRODUCTION: Pleomorphic xanthoastrocytoma (PXA) is a rare subset of circumscribed astrocytic glioma. While PXA typically has a favorable prognosis, anaplastic (WHO Grade III) PXA (aPXA) has a poorer prognosis. Molecular analysis of PXA often reveals BRAF mutations or CDKN2A/B homozygous deletions. NTRK fusions have been identified in a few cases of pediatric gliomas including PXA. BEND-5 gene alterations have been rarely reported in CNS tumors such as glioblastoma but have not been previously reported in PXA. Case Presentation The patient is a 24-year-old female with history of nasopharyngeal embryonal rhabdomyosarcoma treated with chemotherapy and radiation at age 3. She was tested for Li-Fraumeni Syndrome and was reportedly negative. One year ago, she presented with visual changes and was found to have an occipital aPXA. She underwent a gross total resection but declined further treatment with radiation. Next-generation sequencing (NGS) identified a BEND5-NTRK2 fusion, and she began treatment with Larotrectinib. Serial MRI scans have shown no evidence of disease recurrence. Discussion Pediatric patients are at increased risk for glioma after radiation which is age- and dose/volume-dependent. Radiation-induced gliomas are typically higher grade, present in atypical sites, and have a poor prognosis. Development of PXA following radiation is rare but has been reported. Our patient was diagnosed with aPXA almost 20 years after initial treatment for rhabdomyosarcoma. Her aPXA exhibited a BEND5-NTRK2 fusion and lacked classical BRAF alterations and CDKN2A/B deletions that are present in de novo cases. A Neuro-Onc Panel did not identify her fusion or include testing for BEND5 alterations. However, an expanded RNA Exome Fusion Panel NGS identified a unique fusion, which opened her up to targeted treatment with an NTRK inhibitor. Our patient is now 1 year from resection without disease progression on larotrectinib. This case highlights the importance of expanded NGS testing, particularly in rare tumors.

THU108 Pituitary Carcinoma Diagnosed After Ten Years Of Smoldering Ectopic Nasopharyngeal Cushing’s

Abstract Disclosure: L. Carafone: None. E. Vates: None. M. Johnson: None. I. Shafiq: None. Introduction: Pituitary carcinomas are rare and typically carry a poor prognosis. Diagnosis of pituitary carcinoma is made when there is metastasis to one or more sites distant from the pituitary, including craniospinal or systemic metastases. Clinical Case: A 54-year-old man presented to the endocrine clinic in 2011 with recurrent urinary tract infections, thoracic compression fractures, uncontrolled hypertension with hypokalemia, and weight gain. Examination revealed facial plethora, supraclavicular fat pad, central obesity, multiple ecchymoses, proximal muscle weakness and muscle atrophy of the upper and lower extremities. Workup demonstrated abnormal 1 mg overnight dexamethasone suppression test (cortisol after 1 mg dexamethasone 25.7 mcg/dL, n≤1.8 mcg/dL), elevated salivary cortisol (4340 and 2950 ng/dL, n≤99 ng/dL), elevated 24 hr urinary-free cortisol (271.7 mcg/24hr, n≤60 mcg/24 hr), and elevated ACTH (240 pg/mL, n≤46 pg/mL). MRI brain showed a large, lobulated mass in the sphenoid sinus adjacent to the inferior left lateral aspect of the pituitary fossa. He underwent surgical resection of the mass and pathology was consistent with pituitary adenoma, corticotroph cell type. Following surgery, laboratory studies showed normal salivary cortisol (<50 ng/dL, n≤99 ng/dL) and 24 hr urinary-free cortisol (22.4 mcg/24hr, n≤60 mcg/24 hr). After two years of sustained remission, he experienced local recurrence for which he underwent repeat surgery with subsequent remission. One year later, this was again followed by recurrence for which he was treated with intensity-modulated radiation therapy and medical therapies including cabergoline, ketoconazole and eventually metyrapone. Six years after the second surgery, MRI showed increasing heterogeneous enhancement at the postoperative site, and he underwent a third surgery with tumor resection and the same pathology results as the initial resection. He was subsequently treated with fractionated proton therapy. He continued to require metyrapone to manage hypercortisolism despite reassuring serial MRI scans. A right neck mass was palpated in 2022 and CT demonstrated a right level 2b lymph node measuring 2.3 x 1.8 x 2.3 cm. FNA revealed neoplastic cells and he underwent right neck dissection with excision of the lymph node. Pathology was consistent with pituitary tumor, corticotroph cell type. Given metastasis of the pituitary tumor to a cervical lymph node, a diagnosis of pituitary carcinoma was made. Conclusion: The time course in pituitary carcinoma is highly variable from the initial diagnosis of the pituitary tumor to the diagnosis of metastatic disease. In this case, the diagnosis of pituitary carcinoma was made nearly one decade after the initial identification of a pituitary tumor. Metastatic disease should be considered in aggressive pituitary tumors when biochemical and radiologic findings are discordant. Presentation: Thursday, June 15, 2023

P08 Appearance matters: a case of adult-onset Parry-Romberg syndrome with linear scleroderma en coup de sabre and neurological involvement

Abstract Introduction We describe the case of an adult patient who initially presented with neurological symptoms. Investigations were suggestive of a neuroinflammatory disorder but the diagnosis was unclear. It was only as time passed that the cutaneous signs and symptoms of Parry-Romberg syndrome (PRS) and linear scleroderma en coup de sabre (LSCS) became apparent to clinicians as the underlying cause for her presentation. Case description This female patient, with no past medical history, presented in 2015 when she was 43 years old. She reported a one-day history of malaise and lethargy, left-sided headache, numbness affecting the right face and right arm and dysphasia. Her symptoms gradually improved over the following few days. An MRI brain showed extensive T2 hyperintensity in the right frontal and frontoparietal regions. Cerebrospinal fluid (CSF) showed a lymphocytosis and oligoclonal bands, which were present in the CSF only. A repeat MRI brain a few weeks later showed slightly less extensive changes. This was treated by neurologists as a neuroinflammatory disorder with intravenous methylprednisolone pulses. At follow-up, she mentioned that she had noticed a change in her appearance, with the right side of her face becoming increasingly asymmetrical over the last few years. Neurologists were puzzled regarding the diagnosis, but given that she was almost asymptomatic at review, they decided to monitor her with serial MRI scans. There were no further neurological episodes and no interval changes on repeat scans. In 2020, she was referred to ophthalmology, as she had noticed that her right eye had become increasingly sunken. MRI of the orbits and sinuses was reported to show enophthalmos of no obvious cause. Around the same time, she was also referred to dermatology for an enlarging patch of alopecia over the right frontoparietal scalp. Autoimmune screening blood tests including ANA, ENA, dsDNA and centromere were negative. Scalp biopsy was inconclusive but was most in keeping with old alopecia areata. She was treated with intralesional steroids and had a partial response. It was only by 2021 that PRS with LSCS was recognised as the cause of her symptoms. We can be confident that her neuroinflammation is an extracutaneous manifestation, which occurred early on when cutaneous signs were subtle. Discussion PRS is a rare, acquired disorder characterised by progressive unilateral atrophy of facial skin, soft tissue, muscles, and underlying bony structures. LSCS is a subtype of linear scleroderma that occurs on the forehead or frontoparietal scalp. PRS and LSCS commonly coexist, and it is debated whether they are on a spectrum of the same disease. Both usually occur in childhood or adolescence, and adult-onset disease is very rare. The diagnoses are clinical and there are no specific diagnostic tests. Both are associated with neurological involvement, including seizures, headaches, focal neurological deficits and neuropsychiatric changes. Usually, the cutaneous lesion develops months to years before the onset of neurological symptoms. Our patient had noticed subtle changes in her appearance at least five years before her presentation in 2015. Neuroimaging abnormalities are predominately ipsilateral to the cutaneous lesions but may rarely be contralateral. Key learning points Given that adult-onset PRS and LSCS are very rare, there may be a lack of awareness of the conditions amongst adult physicians. This can lead to diagnostic delay. This case highlights that PRS and LSCS are not just conditions of the skin and connective tissues and that neurological involvement is a frequent extracutaneous manifestation. This case is also a reminder of the importance of a thorough examination of the skin, especially when the diagnosis is unclear.

MRI-based vertebral bone quality score: relationship with age and reproducibility.

The purposes of this study were to determine whether VBQ score increased with age and whether VBQ remained consistent across serial MRI studies obtained within 3months. This retrospective study evaluated 136 patients, age 20-69, who received two T1-weighted lumbar MRI within 3months of each other between January 2011 and December 2021. VBQ(L1-4) score was calculated as the quotient of L1-L4 signal intensity (SI) and L3 cerebral spinal fluid (CSF) SI. VBQ(L1) score was calculated as the quotient of L1 SI and L1 CSF SI. Regression analysis was performed to determine correlation of VBQ(L1-4) score with age. Coefficient of variation (CV) was used to determine reproducibility between VBQ(L1-4) scores from serial MRI scans. One hundred thirty-six patients (mean ± SD age 44.9 ± 12.5years; 53.7% female) were included in this study. Extrinsic factors affecting the VBQ score included patient age, MRI relaxation time, and specific MRI machine. When controlling for MRI relaxation/echo time, the VBQ(L1-4) score was positively correlated with age and had excellent reproducibility in serial MRI with CV of 0.169. There was excellent agreement (ICC > 0.9) of VBQ scores derived from the two formulas, VBQ(L1) and VBQ(L1-4). Extrinsic factors, including MRI technical factors and age, can impact the VBQ(L1-4) score and must be considered when using this tool to estimate bone mineral density (BMD). VBQ(L1-4) score was positively correlated with age. Reproducibility of the VBQ(L1-4) score across serial MRI is excellent especially when controlling for technical factors, supporting use of the VBQ score in estimating BMD. The VBQ(L1) score was a reliable alternative to the VBQ(L1-4) score.

Translational Orthotopic Models of Glioblastoma Multiforme.

Genetically engineered mouse (GEM) models for human glioblastoma multiforme (GBM) are critical to understanding the development and progression of brain tumors. Unlike xenograft tumors, in GEMs, tumors arise in the native microenvironment in an immunocompetent mouse. However, the use of GBM GEMs in preclinical treatment studies is challenging due to long tumor latencies, heterogeneity in neoplasm frequency, and the timing of advanced grade tumor development. Mice induced via intracranial orthotopic injection are more tractable for preclinical studies, and retain features of the GEM tumors. We generated an orthotopic brain tumor model derived from a GEM model with Rb, Kras, and p53 aberrations (TRP), which develops GBM tumorsdisplaying linear foci of necrosis by neoplastic cells, and dense vascularization analogous to human GBM. Cells derived from GEM GBM tumors are injected intracranially into wild-type, strain-matched recipient mice and reproduce grade IV tumors, therefore bypassing the long tumor latency period in GEM mice and allowing for the creation of large and reproducible cohorts for preclinical studies. The highly proliferative, invasive, and vascular features of the TRP GEM model for GBM are recapitulated in the orthotopic tumors, and histopathology markers reflect human GBM subgroups. Tumor growth is monitored by serial MRI scans. Due to the invasive nature of the intracranial tumors in immunocompetent models, carefully following the injection procedure outlined here is essential to prevent extracranial tumor growth.

Abstract WMP76: Carotid Revascularization Slows Hemispheric White Matter Disease Progression

Introduction: Carotid revascularization is known to prevent stroke in patients with high-grade carotid stenosis, but whether carotid revascularization may slow the progression of hemispheric WMD in patients with carotid stenosis to prevent cognitive decline have not been well described. Methods: We conducted a longitudinal study involving patients age ≥40 years with carotid stenosis on ultrasound from 2011-2015 with serial brain MRI scans at least 1 year apart followed for radiographic and clinical outcomes to 2020. Severity of carotid stenosis was defined as moderate 50-69%, high-grade 70-99%, or occluded. Hemispheric WMD volume was quantified from axial T2 FLAIR images. Patients were stratified by revascularization status. Primary outcome was change in WMD volume per year ipsilateral or contralateral to the index carotid. Hemispheric differences in the annual rate of WMD progression (cc/yr) were compared between revascularized vs not revascularized using multivariable linear regression analysis adjusted for variables that differed between revascularization status. Results: Of the 150 patients, moderate stenosis was present in 37.3%, high-grade stenosis in 42.0%, and carotid occlusion in 20.7%. Mean age was 71±10 years, 36.7% were female. Seventy-three (48.7%) had carotid revascularization with a median follow-up of 5.1 years. Baseline WMD volume was 4.86cc ipsilateral and 4.39cc contralateral to the index carotid. Patients who underwent revascularization trended to have slower WMD progression in the hemisphere ipsilateral to the index carotid compared to those not revascularized (0.32cc/yr vs 0.63 cc/yr, p=0.340). The same trend was not observed in the contralateral hemisphere. In adjusted models, carotid revascularization was associated with a 0.33 cc per year decrease in WMD progression between hemispheres compared to those not revascularized (β= -0.33, p=0.070). Conclusions: In this study with a median follow-up of 5 years, we found that carotid revascularization resulted in a 50% reduction in the annual rate of WMD progression. Intervention trials should test whether carotid revascularization slows WMD progression in patients with cognitive impairment to prevent further cerebrovascular events and cognitive decline.

A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology.

Stereotactic body radiotherapy (SBRT) is a precise and conformal treatment modality used in the management of metastatic spine tumors. Multiple studies have demonstrated its safety and efficacy for pain and tumor control. However, no uniform quantitative imaging methodology exists to evaluate response to treatment in these patients. This study presents radiographic local control rates post-SBRT, systematically compares measurements acquired according to WHO and Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and explores the relationship to patient outcome. The authors performed a retrospective review of prospectively obtained data from a cohort of 59 consecutive patients (81 metastatic isocenters) treated with SBRT and followed with serial MRI scans. Measurements were performed by a neuroradiologist blinded to the patients' clinical course. Local control status was determined according to both WHO and RECIST measurements, and agreement between the measuring methodologies was calculated and reported. Eighty-one isocenters (111 vertebral bodies) were treated with SBRT. The mean treatment dose was 13.96 Gy and the median follow-up duration was 10.8 months, during which 408 MRI scans were evaluated with both WHO and RECIST criteria for each scan point. Imaging demonstrated a mean unidimensional size decrease of 0.2 cm (p = 0.14) and a mean area size decrease of 0.99 cm2 (p = 0.03). Although 88% of the case classifications were concordant and the agreement was significant, WHO criteria were found to be more sensitive to tumor size change. The local control rates according to WHO and RECIST were 95% and 98%, respectively. Although WHO volumetric measurements are admittedly superior for tumor size measurement, RECIST is simpler, reproducible, and for the first time is shown here to be comparable to WHO criteria. Thus, the application of RECIST methodology appears to be a suitable standard for evaluating post-SBRT treatment response. Moreover, using comprehensive and consistent measuring approaches, this study substantiates the efficacy of SBRT in the treatment of spine metastases.

Assessment of Interfraction Change in Gross Tumor Volume of Anal Carcinoma Patients Undergoing Curative Chemoradiotherapy

<h3>Purpose/Objective(s)</h3> Radiation with concurrent chemotherapy (CRT) represents standard definitive therapy for anal cancer. CRT protocols result in excellent local control but are associated with significant acute and late morbidity. Adaptive planning techniques may allow for decrease in treatment volume and reduce toxicity. In this study, we used serial MRI scans to assess changes in gross tumor volume (GTV) during curative CRT. <h3>Materials/Methods</h3> Since 2019, we have instituted a REB-approved prospective registry study of de-escalated radiotherapy for patients undergoing CRT for anal cancer. Patients received a total dose of 45-63 Gy in 25-35 fractions with concurrent Capecitabine and a single dose of Mitomycin-C on day 1. In addition to pre-treatment (pre-tx) CT and MR simulation, patients also underwent MR simulation at fraction 11 (fx11) and fraction 21 (fx21). The GTV was contoured separately on individual axial T2 sequences. Median (inter-quartile-range) was used for descriptive statistics and the Mann-Whitney-Wilcoxon was used between groups of interfractional contours to determine statistically significant differences in tumor size between fractions. The Kruskal-Wallace test was used to determine significance between all 3 GTV volumes. P-values of <0.05 were considered statistically significant. <h3>Results</h3> A total of 24 patients were accrued. All patient completed RT without interruptions. All 24 had pre-tx MRI. During CRT course, 22 had a second MRI scan (fx11), and 19 had a third (fx21) scan. Table 1 shows the median (IQR) pre-tx GTV and the absolute and percent reduction in the GTV at fx11 and fx21 compared to pre-treatment GTV. Median (IQR) reduction in GTV between pre-tx and fx11 and fx21 MRI was 6.1cc (3.8-12.1) and 7.8cc (5.7-14.6), respectively. Median reduction in GTV between fx11 and fx21 was 2.9cc (1.3-6.6). After normalizing volumes as the percentage of pre-tx GTV, median (IQR) volume was 62.5% (51.6-69.7) (p<0.001) at fx11 and 43.6% (34.2-55.6) (p<0.001) at fx21. Based on Kruskal-Wallace test, overall change between GTVs at all 3 time points was found to be significant, p=0.042. <h3>Conclusion</h3> For patients undergoing CRT for anal cancer, there appears to be an early and significant reduction in the tumor volume over time. This study helps define planning adaptation parameters using serial MRI during CRT and will inform strategies to reduce normal tissue exposure

Perivascular spaces as a marker of disease severity and neurodegeneration in patients with behavioral variant frontotemporal dementia.

Behavioural Variant Frontotemporal Dementia (bvFTD) is a rapidly progressing neurodegenerative proteinopathy. Perivascular spaces (PVS) form a part of the brain's glymphatic clearance system. When enlarged due to poor glymphatic clearance of toxic proteins, PVS become larger and more conspicuous on MRI. Therefore, enlarged PVS may be a useful biomarker of disease severity and progression in neurodegenerative proteinopathies such as bvFTD. This study aimed to determine the utility of PVS as a biomarker of disease progression in patients with bvFTD. Serial baseline and week 52 MRIs acquired from ten patients with bvFTD prospectively recruited and followed in a Phase 1b open label trial of sodium selenate for bvFTD were used in this study. An automated algorithm quantified PVS on MRI, which was visually inspected and validated by a member of the study team. The number and volume of PVS were extracted and mixed models used to assess the relationship between PVS burden and other measures of disease (cognition, carer burden scale, protein biomarkers). Additional exploratory analysis investigated PVS burden in patients who appeared to not progress over the 12 months of selenate treatment (i.e., "non-progressors"). Overall, PVS cluster number (ß = -3.27, CI [-7.80 - 1.27], p = 0.267) and PVS volume (ß = -36.8, CI [-84.9 - 11.3], p = 0.171) did not change over the paired MRI scans 12 months apart. There was association between cognition total composite scores and the PVS burden (PVS cluster ß = -0.802e-3, CI [9.45e - 3 - -6.60e - 3, p ≤ 0.001; PVS volume ß = -1.30e - 3, CI [-1.55e - 3 - -1.05e - 3], p ≤ 0.001), as well as between the change in the cognition total composite score and the change in PVS volume (ß = 4.36e - 3, CI [1.33e - 3 - 7.40e - 3], p = 0.046) over the trial period. There was a significant association between CSF t-tau and the number of PVS clusters (ß = 2.845, CI [0.630 - 5.06], p = 0.036). Additionally, there was a significant relationship between the change in CSF t-tau and the change in the number of PVS (ß = 1.54, CI [0.918 - 2.16], p < 0.001) and PVS volume (ß = 13.8, CI [6.37 - 21.1], p = 0.003) over the trial period. An association was found between the change in NfL and the change in PVS volume (ß = 1.40, CI [0.272 - 2.52], p = 0.045) over time. Within the "non-progressor" group (n = 7), there was a significant relationship between the change in the CSF total-tau (t-tau) levels and the change in the PVS burden (PVS cluster (ß = 1.46, CI [0.577 - 2.34], p = 0.014; PVS volume ß = 14.6, CI [3.86 - 25.4], p = 0.032) over the trial period. Additionally, there was evidence of a significant relationship between the change in NfL levels and the change in the PVS burden over time (PVS cluster ß = 0.296, CI [0.229 - 0.361], p ≤ 0.001; PVS volume ß = 3.67, CI [2.42 - 4.92], p = 0.002). Analysis of serial MRI scans 12 months apart in patients with bvFTD demonstrated a relationship between PVS burden and disease severity as measured by the total cognitive composite score and CSF t-tau. Further studies are needed to confirm PVS as a robust marker of neurodegeneration in proteinopathies.

Evaluating the use of synthetic T1-w images in new T2 lesion detection in multiple sclerosis.

The assessment of disease activity using serial brain MRI scans is one of the most valuable strategies for monitoring treatment response in patients with multiple sclerosis (MS) receiving disease-modifying treatments. Recently, several deep learning approaches have been proposed to improve this analysis, obtaining a good trade-off between sensitivity and specificity, especially when using T1-w and T2-FLAIR images as inputs. However, the need to acquire two different types of images is time-consuming, costly and not always available in clinical practice. In this paper, we investigate an approach to generate synthetic T1-w images from T2-FLAIR images and subsequently analyse the impact of using original and synthetic T1-w images on the performance of a state-of-the-art approach for longitudinal MS lesion detection. We evaluate our approach on a dataset containing 136 images from MS patients, and 73 images with lesion activity (the appearance of new T2 lesions in follow-up scans). To evaluate the synthesis of the images, we analyse the structural similarity index metric and the median absolute error and obtain consistent results. To study the impact of synthetic T1-w images, we evaluate the performance of the new lesion detection approach when using (1) both T2-FLAIR and T1-w original images, (2) only T2-FLAIR images, and (3) both T2-FLAIR and synthetic T1-w images. Sensitivities of 0.75, 0.63, and 0.81, respectively, were obtained at the same false-positive rate (0.14) for all experiments. In addition, we also present the results obtained when using the data from the international MSSEG-2 challenge, showing also an improvement when including synthetic T1-w images. In conclusion, we show that the use of synthetic images can support the lack of data or even be used instead of the original image to homogenize the contrast of the different acquisitions in new T2 lesions detection algorithms.

Conservative treatment for patients with massive prolapsed lumber intervertebral discs

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; The natural history of Lumber hernia of nucleus pulpous is not fully known and absolute indications for surgical intervention cannot be established. Several studies have shown that the most giant discs appear to have the greatest tendency to resolve with conservative treatment. The objective of this study is to investigate whether massive prolapsed discs can be safely managed conservatively once clinical improvement has occurred.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Thirty-five patients were studied by clinical assessments and serial magnetic imaging over 3 years. Patients present with intense sciatica but began to show clinical improvement despite massive disc prolapsed. Clinical assessment included the Lasegue test and neurological improvement. The Oswestry disability index was used to measure function and changes in function. Serial MRI studies allowed the measurement of volume changes of the prolapsed disc material over some time. &lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Initial follow-up at an average of 13.2 months showed that 87% had complete and sustained recovery at the initial follow-up. Only four patients required surgery. The average Oswestry disability index improved from 63% to 20%. Volumetric analysis of serial MRI scans showed an average reduction of 69% in disc size. &lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;A massive disc prolapsed can pursue a favourable course. If early progress is shown, the long-term prognosis is very good and even massive disc prolapses can be treated conservatively.&lt;/p&gt;

Elevated intraspinal pressure drives edema progression after acute compression spinal cord injury in rabbits

Elevated intraspinal pressure (ISP) following traumatic spinal cord injury (tSCI) can be an important factor for secondary SCI that may result in greater tissue damage and functional deficits. Our present study aimed to investigate the dynamic changes in ISP after different degrees of acute compression SCI in rabbits with closed canals and explore its influence on spinal cord pathophysiology. Closed balloon compression injuries were induced with different inflated volumes (40 μl, 50 μl or no inflation) at the T7/8 level in rabbits. ISP was monitored by a SOPHYSA probe at the epicenter within 7 days post-SCI. Edema progression, spinal cord perfusion and damage severity were evaluated by serial multisequence MRI scans, somatosensory evoked potentials (SEPs) and behavioral scores. Histological and blood spinal cord barrier (BSCB) permeability results were subsequently analyzed. The results showed that the ISP waveforms comprised three peaks, significantly increased after tSCI, peaked at 72 h (21.86 ± 3.13 mmHg) in the moderate group or 48 h (31.71 ± 6.02 mmHg) in the severe group and exhibited “slow elevated and fast decreased” or “fast elevated and slow decreased” dynamic changes in both injured groups. Elevated ISP after injury was correlated with spinal cord perfusion and edema progression, leading to secondary lesion enlargement. The secondary damage aggravation can be visualized by diffusion tensor tractography (DTT). Moreover, the BSCB permeability was significantly increased at the epicenter and rostrocaudal segments at 72 h after SCI; by 14 days, notable permeability was still observed at the caudal segment in the severely injured rabbits. Our results suggest that the ISP of rabbits with closed canals increased after acute compression SCI and exhibited different dynamic change patterns in moderately and severely injured rabbits. Elevated ISP exacerbated spinal cord perfusion, drove edema progression and led to secondary lesion enlargement that was strongly associated with BSCB disruption. For severe tSCI, early intervention targeting elevated ISP may be an indispensable choice to rescue spinal cord function.

Post-operative MRI detection of residual cholesteatoma in pediatric patients - The yield of serial scans over a long follow-up

ObjectivesNon-echo-planar diffusion weighted magnetic resonance imaging (Non-EPI DWI MRI) is commonly used for follow-up after cholesteatoma surgery. MRI has a critical role in the evaluation of residual disease, where physical examination will commonly demonstrate an intact tympanic membrane. The aim of our study was to assess the timing of residual cholesteatoma identification on serial MRI scans and the yield of MRI follow up after canal wall up tympano-mastoidectomy. MethodsA retrospective chart review of children that underwent canal wall up tympano-mastoidectomy due to cholesteatoma in Schneider Children's Medical Center during 2004–2016, and were followed up both clinically and with MRI. ResultsSeventy-seven children (89 ears) were included, who altogether underwent 166 surgeries (77 revisions). Average follow-up was 66 ± 34.4 months. During follow up, 244 scans were performed; 19 cases of residual disease were diagnosed by MRI and confirmed in surgery. The mean time from surgery and an MRI positive for residual disease was 29.7 ± 16 months (range: 10–66). In 9/19 cases (47%), at least one negative MRI preceded the scan positive for residual disease, and in 4 cases at least two initial scans were negative. ConclusionsMRI plays an important role in the diagnosis of residual disease after cholesteatoma surgery. In our cohort. Almost half of the cases diagnosed with residual disease had at least one negative scan prior to the positive one, emphasizing the importance of close radiological follow-up with serial scans after surgery.

Early Metabolic Changes in 1H-MRSI Predictive for Survival in Patients With Newly Diagnosed High-grade Glioma.

The purpose of this study was to evaluate the association of specific threshold values for changes in metabolic metrics measured from 1H magnetic resonance spectroscopic imaging (MRSI) to survival of patients with high-grade glioma treated with multimodality therapy. Forty-four patients with newly diagnosed high-grade glioma were prospectively enrolled. Serial MRI and MRSI scans provided measures of tumor choline, creatine, and N-acetylaspartate (NAA). Cox regression analyses adjusted for patient age, KPS, and delivery of concurrent chemotherapy were used to assess the association of changes in metabolic metrics with survival. Median follow-up time for patients at risk was 13.4 years. Overall survival (OS) was longer in patients with ≤20% increase (vs. >20%) in normalized choline (p=0.024) or choline/NAA (p=0.024) from baseline to week 4 of RT. During this period, progression-free survival (PFS) was longer in patients with ≤40% increase (vs. >40%) in normalized choline (p=0.013). Changes in normalized creatine, choline/creatine, and NAA/creatine from baseline to mid-RT were not associated with OS. From baseline to post-RT, changes in metabolic metrics were not associated with OS or PFS. Threshold values for serial changes in choline metrics on mid-RT MRSI associated with OS and PFS were identified. Metabolic metrics at post-RT did not predict for these survival endpoints. These findings suggest a potential clinical role for MRSI to provide an early assessment of treatment response and could enable risk-adapted therapy in clinical trial development and clinical practice.

Assessing the effect of anesthetic gas mixtures on hyperpolarized 13 C pyruvate metabolism in the rat brain.

PurposeTo determine the effect of altering anesthetic oxygen protocols on measurements of cerebral perfusion and metabolism in the rodent brain.MethodsSeven rats were anesthetized and underwent serial MRI scans with hyperpolarized [1–13C]pyruvate and perfusion weighted imaging. The anesthetic carrier gas protocol used varied from 100:0% to 90:10% to 60:40% O2:N2O. Spectra were quantified with AMARES and perfusion imaging was processed using model‐free deconvolution. A 1‐way ANOVA was used to compare results across groups, with pairwise t tests performed with correction for multiple comparisons. Spearman's correlation analysis was performed between O2% and MR measurements.ResultsThere was a significant increase in bicarbonate:total 13C carbon and bicarbonate:13C pyruvate when moving between 100:0 to 90:10 and 100:0 to 60:40 O2:N2O % (0.02 ± 0.01 vs. 0.019 ± 0.005 and 0.02 ± 0.01 vs. 0.05 ± 0.02, respectively) and (0.04 ± 0.01 vs. 0.03 ± 0.01 and 0.04 ± 0.01 vs. 0.08 ± 0.02, respectively). There was a significant difference in 13C pyruvate time to peak when moving between 100:0 to 90:10 and 100:0 to 60:40 O2:N2O % (13 ± 2 vs. 10 ± 1 and 13 ± 2 vs. 7.5 ± 0.5 s, respectively) as well as significant differences in cerebral blood flow (CBF) between gas protocols. Significant correlations between bicarbonate:13C pyruvate and gas protocol (ρ = −0.47), mean transit time and gas protocol (ρ = 0.41) and 13C pyruvate time‐to‐peak and cerebral blood flow (ρ = −0.54) were also observed.ConclusionsThese results demonstrate that the detection and quantification of cerebral metabolism and perfusion is dependent on the oxygen protocol used in the anesthetized rodent brain.

Towards a fully automatic AI framework to calculate voxel‐wise atrophy in the human brain

AbstractBackgroundLongitudinal changes in volume using co‐registration of two serial T1W MRI scans are used as biomarkers to track the development of Alzheimer’s Disease and monitor potential treatment effects. Current methods (e.g., the boundary shift integral, BSI) may be restricted to certain regions or are computationally intensive and slow (e.g., the Advanced Normalization Tools, ANTs).MethodWe present an AI‐based framework to calculate voxel‐wise atrophy in the human brain. Our method features convolutional neural networks for cross‐sectional semantic segmentation and longitudinal pairwise non‐linear registration which does not require subject‐specific optimization. It warps one image to another by minimizing their difference, while preserving topology. Voxel‐wise volume change is estimated using the Jacobian determinant of the warp field, summed within a specified and automatically segmented region of interest in the baseline image. We evaluate our framework in ADNI (40 HC and 40 MCI) and OASIS3 (100 HC and 100 MCI) participants and assess the method’s measures of annualized atrophy in whole brain, ventricles, and hippocampus using common language effect sizes (CLES) and a Mann‐Whitney U‐test. Retest variability is measured in 30 OASIS3 participants with two serial MR scans not more than 13 days apart. We compare results to BSI as well as the same framework but substituting the non‐linear registration part with ANTs.ResultOur algorithm outperforms ANTs in non‐linear registration accuracy with mean (SD) normalized mutual information of 0.746 (0.055) compared to 0.651 (0.052) for ANTs and 0.646 (0.049) with affine registration only. It also has lower retest variability than ANTs (mean variability range is 0.08%‐0.12% and 0.15%‐0.34% for our algorithm and ANTs respectively). Finally, both BSI and our method show significant group difference for whole brain, ventricles, and hippocampus (all p &lt; 0.002, CLES &gt; 0.69) in both datasets, whereas in ANTs there is no significant group effect for hippocampus (p = 0.12) (see Table 1 for all results).ConclusionOur framework produces fast (seconds) and accurate non‐linear registration and voxel‐wise atrophy calculation for two serial MR images. Our calculated atrophy values show sensitivity to clinical diagnosis in cognitively impaired patients, comparable to current state‐of‐the‐art methods.