Sequential Magnetic Resonance Imaging Scans Research Articles

Prediction of treatment response after stereotactic radiosurgery of brain metastasis using deep learning and radiomics on longitudinal MRI data

We developed artificial intelligence models to predict the brain metastasis (BM) treatment response after stereotactic radiosurgery (SRS) using longitudinal magnetic resonance imaging (MRI) data and evaluated prediction accuracy changes according to the number of sequential MRI scans. We included four sequential MRI scans for 194 patients with BM and 369 target lesions for the Developmental dataset. The data were randomly split (8:2 ratio) for training and testing. For external validation, 172 MRI scans from 43 patients with BM and 62 target lesions were additionally enrolled. The maximum axial diameter (Dmax), radiomics, and deep learning (DL) models were generated for comparison. We evaluated the simple convolutional neural network (CNN) model and a gated recurrent unit (Conv-GRU)-based CNN model in the DL arm. The Conv-GRU model performed superior to the simple CNN models. For both datasets, the area under the curve (AUC) was significantly higher for the two-dimensional (2D) Conv-GRU model than for the 3D Conv-GRU, Dmax, and radiomics models. The accuracy of the 2D Conv-GRU model increased with the number of follow-up studies. In conclusion, using longitudinal MRI data, the 2D Conv-GRU model outperformed all other models in predicting the treatment response after SRS of BM.

The relationship between subchondral bone cysts and cartilage health in the Tibiotalar joint: A finite element analysis

BackgroundSubchondral bone cysts are a common presentation in ankle haemarthropathy. The relationship with ankle joint health has however not previously been investigated. The aim of this study was to assess the influence of subchondral bone cysts of differing shapes, volumes and depths on joint health. MethodsChronologically sequential Magnetic Resonance imaging scans of four hemophilic ankles with subchondral bone cysts present (N = 18) were used to build patient specific finite element models under two cystic conditions to assess their influence on cartilage contact pressures. Variables such as location, volume and depth were considered individually, to investigate whether certain cystic conditions may be more detrimental to cartilage health. FindingsSignificant quantifiable contact redistribution was seen in the presence of subchondral bone cysts and this redistribution reflected the shape and size of the cysts, however, with the presence of cysts in both bones in 10 of the 18 cases a direct relationship to volume could not be correlated. InterpretationThis work demonstrated a redistribution of contact pressures in the presence of subchondral bone cysts. This alteration to loading history could be linked to cartilage degeneration due to the biological response to abnormal loading.

Atypical Presentation of Anti-NMDAR encephalitis in a Male Patient – an Unfortunate Mimic

Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuroinflammatory disorder with a predilection for females. Males present differently, with seizures rather than the better-recognized constellation of psychiatric and behavioral symptoms dominating the initial stages of the disease, providing a potential substrate for delayed recognition and treatment. Case Presentation An 18-year-old man presented with fever and “seizures. When examined, he was febrile but alert and coherent. His neurologic, respiratory, cardiovascular, and abdominal examinations were unremarkable. Diagnosed with infective meningoencephalitis, he was started on intravenous ceftriaxone and acyclovir concurrently with anti-epileptic medications. However, he deteriorated into refractory status epilepticus. Electroencephalograms showed left temporo-parietal seizures. Cerebrospinal fluid analysis revealed inflammatory features, but the virologic assays and bacterial cultures returned negative. Magnetic resonance imaging scans performed in the first and second week from symptom-onset demonstrated the interval development of widespread sulcal T2 hyperintensity, with florid and diffuse leptomeningeal enhancement. Anti-NMDAR antibodies were subsequently detected in his cerebrospinal fluid by indirect immunofluorescence. Diagnosed with anti-NMDAR encephalitis, he received plasmapheresis, methylprednisolone and immunoglobulin infusions. Conclusion Anti-NMDAR encephalitis should be considered in patients, especially males, who are treated for suspected infectious meningoencephalitis, but continue to deteriorate, even in the absence of prominent psychiatric or behavioral symptoms, considering how the initial symptoms differ between the genders. The interval development of diffuse and florid leptomeningeal enhancement on sequential magnetic resonance imaging scans of our patient has not been described in prior reports, and may be reflective of the underlying inflammatory processes.

Quantitating Interfraction Target Dynamics During Concurrent Chemoradiation for Glioblastoma: A Prospective Serial Imaging Study

Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study quantifies interfraction dynamics (tumor size, position, and geometry) based on sequential magnetic resonance imaging scans obtained during standard 6-week chemoradiation. Sixty-one patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2/FLAIR axial sequences at planning (Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after the final fraction of chemoradiation therapy (P1M). Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured at all time points. Target dynamics were quantified by absolute volume (V), volume relative to Fx0 (Vrel), and the migration distance (dmigrate; the linear displacement of the GTV or CTV relative to Fx0). Temporal changes were assessed using a linear mixed-effects model. Median volumes at Fx0, Fx10, Fx20, and P1M for the GTV were 18.4 cm3 (range, 1.1-110.5 cm3), 14.7 cm3 (range, 0.9-115.1 cm3), 13.7 cm3 (range, 0.6-174.2 cm3), and 13.0 cm3 (range, 0.9-76.3 cm3), respectively, with corresponding median Vrel of 0.88 at Fx10, 0.77 at Fx20, and 0.71 at P1M relative to Fx0 (P < .001 for all). The GTV (CTV) migration distances were greater than 5 mm in 46% (54%) of patients at Fx10, 50% (58%) of patients at Fx20, and 52% (57%) of patients at P1M. Dynamic tumor morphologic changes were observed, with 40% of patients exhibiting a decreased GTV (Vrel ≤1) with a dmigrate >5 mm during chemoradiation therapy. Clinically meaningful tumor dynamics were observed during chemoradiation therapy for glioblastoma, supporting evaluation of daily MRI guided radiation therapy and treatment plan adaptation.

Tumor pseudoprogression and true progression following gamma knife radiosurgery for recurrent ependymoma

BackgroundGamma knife radiosurgery (GKRS) has become an effective salvage therapeutic option for recurrent ependymomas. However, its effectiveness can be assessed only by neuroimaging before clinical deterioration occurs. We analyzed the evolution of post-GKRS magnetic resonance imaging (MRI) features and sought to establish the feasibility of timely appropriate clinical management of the recurrent tumors. MethodsWe retrospectively investigated 19 recurrent ependymomas of 11 patients treated with GKRS in our hospital from 1994 to 2013. All included tumors had sequential MRI at 3–6-month intervals, and tumor response was volumetrically calculated on consecutive MRI. ResultsPost-GKRS tumors might show an increased enhancement or loss of enhancement associated with tumor enlargement or straight shrinkage. Seven of 19 tumors (37%) had continuously regressed or remained stable up to the last follow-up. Twelve of 19 tumors (63%) showed enlargement of enhancing lesions through examination of the post-GKRS follow-up MRI within the first 18 months. Five of 12 tumors (42%) showed continuous enlargement, which was interpreted as true progression; seven of 12 (58%) exhibited transient increasing enhanced volume that resolved within 6 months, and which was interpreted as pseudoprogression. There was no significant association between the presence of pseudoprogression and the pathological grades or locations of the tumors, and the concomitant chemotherapy or previous radiotherapy. Statistically significant differences were found for mean apparent diffusion coefficient (ADC) values and ADC ratio (prior to and after GKRS) of enhancing lesions between pseudoprogression and true progression. ConclusionThe MRI patterns of post-GKRS recurrent ependymomas are heterogeneous. Transient increased tumor volume may represent pseudoprogression, whose final tumor control rate was not significantly different from those cases with straight tumor shrinkage. ADC values, ADC ratio, and sequential follow-up MRI scans are beneficial to differentiate between pseudoprogression and true progression, and help guide clinical management.

De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy.

ObjectiveTo determine the cause and course of a novel syndrome with progressive encephalopathy and brain atrophy in children.MethodsClinical whole-exome sequencing was performed for global developmental delay and intellectual disability; some patients also had spastic paraparesis and evidence of clinical regression. Six patients were identified with de novo missense mutations in the kinesin gene KIF1A. The predicted functional disruption of these mutations was assessed in silico to compare the calculated conformational flexibility and estimated efficiency of ATP binding to kinesin motor domains of wild-type (WT) versus mutant alleles. Additionally, an in vitro microtubule gliding assay was performed to assess the effects of de novo dominant, inherited recessive, and polymorphic variants on KIF1A motor function.ResultsAll six subjects had severe developmental delay, hypotonia, and varying degrees of hyperreflexia and spastic paraparesis. Microcephaly, cortical visual impairment, optic neuropathy, peripheral neuropathy, ataxia, epilepsy, and movement disorders were also observed. All six patients had a degenerative neurologic course with progressive cerebral and cerebellar atrophy seen on sequential magnetic resonance imaging scans. Computational modeling of mutant protein structures when compared to WT kinesin showed substantial differences in conformational flexibility and ATP-binding efficiency. The de novo KIF1A mutants were nonmotile in the microtubule gliding assay.InterpretationDe novo mutations in KIF1A cause a degenerative neurologic syndrome with brain atrophy. Computational and in vitro assays differentiate the severity of dominant de novo heterozygous versus inherited recessive KIF1A mutations. The profound effect de novo mutations have on axonal transport is likely related to the cause of progressive neurologic impairment in these patients.

Relationship of Bone Mineral Density to Progression of Knee Osteoarthritis

To evaluate the longitudinal relationship between bone mineral density (BMD) and BMD changes and the progression of knee osteoarthritis (OA), as measured by cartilage outcomes. We used observational cohort data from the Vitamin D for Knee Osteoarthritis trial. Bilateral femoral neck BMD values as well as knee magnetic resonance imaging (MRI) scans in each subject were obtained at baseline and subsequently at 12 months and 24 months. The change in total cartilage volume and tibial and femoral cartilage thickness was measured by manual cartilage segmentation of 2 sequential knee MRI scans in each subject. Multivariable linear regression models were used to examine the associations of baseline BMD and BMD change with the cartilage outcomes, adjusting for baseline age, sex, body mass index, malalignment, and vitamin D treatment. Model fit and assumptions were validated. A total of 127 subjects were eligible for analysis. Longitudinal BMD loss was associated with loss of cartilage volume (β = 1.25 per 0.1 gm/cm(2) , P = 0.02) and loss of tibial cartilage thickness (β = 0.028, P = 0.03). BMD loss of a magnitude greater than the least significant change (<-4.7%) was associated with 1.02% cartilage volume loss per year (P = 0.005), 0.014 mm femoral cartilage thickness loss (P = 0.04), and 0.021 mm tibial cartilage thickness loss per year (P = 0.009). There were no significant associations between baseline BMD and any of the cartilage outcomes. Longitudinal BMD loss is associated with progressive cartilage loss in knees with OA. Further work to clarify the basis of this relationship could reveal novel therapeutic targets for knee OA.

De novo Generation of an Axially Vascularized Processed Bovine Cancellous-Bone Substitute in the Sheep Arteriovenous-Loop Model

Background/Aims: The aim of this study was to generate an axially vascularized bone substitute. The arteriovenous (AV)-loop approach in a large-animal model was applied in order to induce axial vascularization in a clinically approved processed bovine cancellous bone (PBCB) matrix of significant volume with primary mechanical stability and to assess the course of increasing axial vascularization. Methods: PBCB constructs were implanted into 13 merino sheep together with a microsurgically created AV loop in an isolation chamber. The vascularization process was monitored by sequential magnetic resonance imaging (MRI) scans. Explants were subjected to micro-computed tomography (micro-CT) analysis, histomorphometry and immunohistochemistry for CD31 and CD45. Results: Increasing axial vascularization in PBCB constructs was quantified by histomorphometry and visualized by micro-CT scans. Intravital sequential MRI scans demonstrated a significant progressive increase in perfused volume within the matrices. Immunohistochemistry confirmed endothelial lining of newly formed vessels. Conclusion: This study demonstrates successful axial vascularization of a clinically approved, mechanically stable bone substitute with a significant volume by a microsurgical AV loop in a large-animal model. Thus microsurgical transplantation of a tissue-engineered, axially vascularized and mechanically stable bone substitute with clinically relevant dimensions may become clinically feasible in the future.

LINEAR ACCELERATOR-BASED STEREOTACTIC RADIOSURGERY FOR BILATERAL VESTIBULAR SCHWANNOMAS IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2

Patients with neurofibromatosis Type 2 (NF2) patients typically have bilateral vestibular schwannomas (VS) and are at risk for developing bilateral deafness, bilateral trigeminal, and bilateral facial nerve function loss. Previous reports suggested that treatment outcomes in these patients are worse compared with those for patients with sporadic solitary VS. Very few reports, however, have been published on linear accelerator-based radiosurgery (RS) and stereotactic radiation therapy (SRT) in patients with NF2. In particular, in patients with NF2 who already have unilateral hearing loss, avoidance of hearing loss on the opposite side poses a challenge for RS and SRT. We studied our treatment results in patients with NF2 with bilateral VS, treated with linear accelerator-based RS and SRT. In 204 patients with VS treated with RS or SRT in Amsterdam starting from 1992, we identified 25 patients with NF2 who had bilateral tumors. Indications for treatment were either tumor progression on sequential magnetic resonance imaging scans and/or progressive hearing loss. Mean tumor diameter was 2.5 cm. Stereotactic irradiation was administered to all patients using five noncoplanar arcs with a single isocenter to a dose of 10 to 12.5 Gy in a single fraction or 20 to 25 Gy in five fractions in 1 week prescribed to the 80% isodose encompassing the tumor. On the untreated side, all patients showed hearing loss and eight (32%) had ipsilateral deafness. Five patients were followed for less than 1 year. Of the remaining 20 patients, five had ipsilateral deafness before treatment. Consequently, 15 patients were at risk for treatment-related hearing loss. They showed a mean pure tone average (PTA) of 51 dB (8-112 dB) before treatment. After treatment all patients were assessed at yearly intervals including magnetic resonance imaging and pure tone audiometry. Median follow-up time was 51 months (12-109 mo). Local tumor control was obtained in all 20 patients, and no treatment-related trigeminal or facial nerve toxicity was observed. Hearing status was assessed yearly after treatment. This assessment revealed that the mean PTA in the 15 hearing patients dropped from 51 to 77 dB (40-120 dB). In six patients (40%) the additional PTA loss ranged from 0 to 15 dB, in another six (40%) it ranged from 15 to 45 dB, and in three of these patients (20%), it was more than 45 dB. No additional hearing loss was observed beyond 36 months after treatment. In this largest series in the literature of linear accelerator-based RS and SRT for VS NF2 patients, excellent local control rates were found with minimal facial and trigeminal nerve toxicity. Although more than 40% of the patients retained their hearing level or lost less than 15 dB of PTA on the irradiated side, preservation of hearing remains a major concern.

Statistical Properties of Jacobian Maps and the Realization of Unbiased Large-Deformation Nonlinear Image Registration

Maps of local tissue compression or expansion are often computed by comparing magnetic resonance imaging (MRI) scans using nonlinear image registration. The resulting changes are commonly analyzed using tensor-based morphometry to make inferences about anatomical differences, often based on the Jacobian map, which estimates local tissue gain or loss. Here, we provide rigorous mathematical analyses of the Jacobian maps, and use themto motivate a new numerical method to construct unbiased nonlinear image registration. First, we argue that logarithmic transformation is crucial for analyzing Jacobian values representing morphometric differences. We then examine the statistical distributions of log-Jacobian maps by defining the Kullback-Leibler (KL) distance on material density functions arising in continuum-mechanical models. With this framework, unbiased image registration can be constructed by quantifying the symmetric KL-distance between the identity map and the resulting deformation. Implementation details, addressing the proposed unbiased registration as well as the minimization of symmetric image matching functionals, are then discussed and shown to be applicable to other registration methods, such as inverse consistent registration. In the results section, we test the proposed framework, as well as present an illustrative application mapping detailed 3-D brain changes in sequential magnetic resonance imaging scans of a patient diagnosed with semantic dementia. Using permutation tests, we show that the symmetrization of image registration statistically reduces skewness in the log-Jacobian map.

White Matter Lesions Are Associated With Progression of Medial Temporal Lobe Atrophy in Alzheimer Disease

Medial temporal lobe atrophy (MTA) is a hallmark of Alzheimer disease (AD). Its progression is often seen during the course of AD, but its frequency and risk factors remain unclear. We investigated MTA in 35 patients with AD from whom sequential magnetic resonance imaging scans were available. White matter lesions (WML; for the periventricular [PV] and subcortical [SC] regions separately) and MTA were rated semiquantitatively. In approximately two thirds of all patients, progression of MTA was found. The mean MTA progression was 0.8 (standard deviation: 0.5) and 0.3 (standard deviation: 0.4) for patients with or without PVWML at baseline (P=0.01). Patients who showed progression of PVWML over the course of their disease had a significantly higher mean progression of MTA than those without PVWML progression (0.9 [SD: 0.4]) and 0.4 [SD: 0.5]; P=0.01). Patients with PVWML at baseline had a 40-fold increased risk for progression of MTA compared with those without baseline PVWML (odds ratio=40.0, 95% CI=1.3 to 1.2x10(3), P=0.03). Patients with progression of PVWML during the course of the disease had an increased risk for MTA progression (odds ratio=3.7 per unit increase of progression of PVWML, 95% CI=1.1 to 12.9, P=0.04). There was higher risk for progression of MTA for those with progression of PVWML than those without (odds ratio=10.9, 95% CI=1.0 to 122.5, P=0.05). This was not found for SCWML. Our findings suggest that the presence and the progression of WML are associated with progression of MTA in AD. WML may be a predictor of the course of the disease and a potential treatment target in AD.

Laparoscopic renal cryoablation in 32 patients

Objectives. Laparoscopic renal cryoablation is a developmental minimally invasive nephron-sparing treatment alternative for highly select patients with small renal tumors. We present our evolving experience with this procedure. Methods. Thirty-two patients (34 tumors) with a mean tumor size of 2.3 cm on preoperative computed tomography underwent laparoscopic renal cryoablation. As dictated by the tumor location, cryoablation was performed by either the retroperitoneal (n = 22) or the transperitoneal (n = 10) laparoscopic approach using real-time ultrasound monitoring. A double freeze-thaw cycle was routinely performed. Results. The mean surgical time was 2.9 hours, cryoablation time 15.1 minutes, and blood loss 66.8 mL. For a mean intraoperative ultrasonographic tumor size of 2 cm, the mean cryolesion size was 3.2 cm. The hospital stay was less than 23 hours in 22 (69%) of 32 patients. Sequential magnetic resonance imaging scans demonstrated a gradual contraction in the mean diameter of the cryolesions. Of the 20 patients who underwent a 1-year follow-up magnetic resonance imaging scan, the cryoablated tumor was no longer visible in 5. Of note, 23 patients have now undergone a 3 to 6-month follow-up computed tomography-directed biopsy of the cryoablated tumor site; the biopsy was negative for cancer in all 23 patients. No evidence of local or port-site recurrence was found during a mean follow-up of 16.2 months. Conclusions. Critical long-term data regarding laparoscopic renal cryoablation, a developmental technique, are awaited. However, our initial experience is cautiously optimistic. Despite its significant potential for false-negative results, it is encouraging that the follow-up computed tomography-directed needle biopsies at 3 to 6 months were negative for cancer in 23 of 23 patients.

Interferons in the treatment of multiple sclerosis: do they prevent the progression of the disease?

HERE IS little doubt that t reatment o f multiple sclerosis (MS) with type 1 interferons reduces the frequency of clinical exacerbations. This observation has been corroborated repeatedly. Treatment of 124 patients with recombinant interferon beta-1b (IFN-b-1b) reduced the frequency of attacks by 33.8%. 1 This reduction was sustained for 5 years but both statistical significance and power were weakened in the later years of the trial, as progressively fewer patients remained in the study. The reduction in the frequency of attacks was associated with a reduction in the severity of attacks, the number of interventions with steroids, and the frequency of hospitalizations. The r eduction i n t he f requency of attacks was modest in comparison with the reduction in activity shown on magnetic resonance imaging (MRI) scans (median, 80% reduction in the number of active scans identified on sequential T2-weighted MRI scans). There was a negligible increase in the burden of disease in patients treated with IFN-b-1b for more than 4 years. 2 The findings from the MRI scans correlated, albeit modestly, with the change in disability scores. 3 Most investigators believed that this clinical and MRI efficacy would have translated into a reduction in the progression of the disease. At the end of 3 years, 20% of patients treated with IFN-b-1b met the definition of confirmed disability (a 3month sustained 1-point increase in score on the Kurtzke Expanded Disability Status Scale) compared with 28% of patients treated with placebo. 1 This difference did not reach statistical significance (P = .16). Several reasons were offered to explain this shortfall in disability outcome. First, the study was neither designed nor powered statistically to identify a moderate effect on disease progression. This would have required more patients and a longer follow-up period. Second, the dosage of IFN-b-1b used in the pivotal study might have been too low. A clear-cut dose response had been associated with the effect of IFNb-1b on attacks in patients with MS. Third, we entertained the possibility that prevention of attacks might be irrelevant to the factors required for slowing the progression of the disease. Even though the indications were favorable, it was conceded that IFNs might not prevent the development of disability in patients with MS. Indeed, in 12 pilot studies in which type 1 IFNs were studied in patients with progressive MS, improvement was identified in patients from only 2, both of which were open-label in design. In 5 studies, patients treated with IFN were thought to worsen, and in another 5 studies, no benefit was identi

Evaluation of post-exercise magnetic resonance images of the rotator cuff.

To examine the effect of strenuous exercise on the magnetic resonance imaging (MRI) characteristics of the rotator cuff tendon. A second objective was to define an optimal time to image the rotator cuff and possibly eliminate exercise-induced false positives. Five male subjects from 24 to 38 years old with normal rotator cuffs by history, physical examination, and screening MRI underwent a rotator cuff exercise session on the Biodex System 2 (Biodex, Shirley, New York). The exercise sessions were followed by sequential MRI scans of the exercised shoulder. These were performed immediately and at 8 h and 24 h after exercise. The rotator cuff tendon and subacromial-subdeltoid bursal signal remained unchanged from the pre-exercise through the 24-h post-exercise scans. The rotator cuff muscle signal was increased in five of five subjects on the immediate post-exercise fat-suppressed T2-weighted images. This signal returned to baseline by the 8-h scan. Positive findings of rotator cuff pathology on MRI after strenuous athletic activity should not be discounted as normal exercise-induced changes. Also, diagnostic MRI scanning may take place after a practice session without an increased risk of false positives.

Magnetic Resonance Imaging for Detecting and Treatment Monitoring of Orthotopic Murine Bladder Tumor Implants

We assessed the feasibility of magnetic resonance imaging (MRI) for detection and treatment monitoring of early stage orthotopic murine bladder (MBT-2) tumor implants. Thirty mice were scheduled for imaging at six, 14, 18 and 21 days after tumor implantation. Using a volume imaging coil, MRI demonstrated very early orthotopic tumors, the detection of which would otherwise have been impossible by clinical signs only. Sequential accurate assessment of tumor size was achieved by inflation of the bladders with a fixed volume of Gadolinium-DTPA contrast. The presence of established MBT-2 intravesical tumors was confirmed by gross pathology and light microscopy of the corresponding whole mount bladder sections. Histological examination of the corresponding tumor specimens revealed the presence of transitional cell bladder carcinoma which correlated very well with the topography and depth of tumor involvement as indicated on MRI. The mice tolerated repeated MR imaging well. Early tumors at day 14 were detectable on MRI (with serial tumor growth to day 21), with no clinical signs of disease. In a subsequent study, response to intravesical tumor necrosis factor alpha (TNF-a) immunotherapy was monitored with serial MRI. The serial MR images from six tumor-bearing mice (three controls and three TNF-a treated) have been selected to illustrate the consistent findings of this study. Sequential MRI scans of TNF-a treated mice revealed retardation of tumor growth that correlated well with the corresponding histologic examination. The orthotopic tumor and MRI model described is ideal for preclinical evaluation of new potential intravesical chemotherapy and immunotherapy agents.