Change In Lesion Volume Research Articles

Efficacy of Platelet-Rich Plasma for the Treatment of Interstitial Supraspinatus Tears: A Double-Blinded, Randomized Controlled Trial

Background: The benefits of platelet-rich plasma (PRP) for the treatment of rotator cuff tears remain inconclusive, as it is administered either as an adjuvant to surgical repair or as a primary infiltration without targeting the index lesion, which could dilute its effect. Purpose: To determine whether PRP infiltrations are superior to saline solution infiltrations (placebo) at improving healing, pain, and function when injected under ultrasound guidance within isolated interstitial supraspinatus tears. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In this single-center, double-blinded, randomized controlled trial, 80 adults with symptomatic isolated interstitial tears of the supraspinatus, confirmed by magnetic resonance arthrography, were randomized to PRP or saline injections. Each patient received 2 injections with a 1-month interval. The primary outcome was the change in lesion volume, calculated on magnetic resonance arthrography, at 7 months. The secondary outcomes were improvements in shoulder pain and the Single Assessment Numerical Evaluation (SANE) score at >12 months. Results: Preoperative patient characteristics did not differ between the 2 groups. At 7 months, there were no significant differences between the PRP and control groups in terms of a decrease in lesion size (–0.3 ± 23.6 mm3 vs –8.1 ± 84.7 mm3, respectively; P = .175); reduction of pain on a visual analog scale (VAS) (–2.3 ± 3.0 vs –2.0 ± 3.0, respectively; P = .586); and improvement in SANE (16.7 ± 20.0 vs 14.9 ± 29.0, respectively; P = .650), Constant (8.6 ± 13.0 vs 10.7 ± 19.0, respectively; P = .596), and American Shoulder and Elbow Surgeons (19.5 ± 20.0 vs 21.9 ± 28.0, respectively; P = .665) scores. At >12 months, there were no significant differences between the PRP and control groups in terms of a reduction of pain on a VAS (–3.3 ± 2.6 vs –2.3 ± 3.2, respectively; P = .087) or improvement in the SANE score (24.4 ± 27.5 vs 23.4 ± 24.9, respectively; P = .846). At 19.5 ± 5.3 months, the incidence of adverse effects (pain >48 hours, frozen shoulder, extension of lesion) was significantly higher in the PRP group than the control group (54% vs 26%, respectively; P = .020). Conclusion: PRP injections within interstitial supraspinatus tears did not improve tendon healing or clinical scores compared with saline injections and were associated with more adverse events. Registration: NCT02672085 (ClinicalTrials.gov identifier).

Volumetric changes of intracranial metastases during the course of fractionated stereotactic radiosurgery and significance of adaptive planning.

Fractionated Gamma Knife surgery (FGKS) has recently been used to treat large brain metastases. However, little is known about specific volume changes of lesions during the course of treatment. The authors investigated short-term volume changes of metastatic lesions during FGKS. The authors analyzed 33 patients with 40 lesions who underwent FGKS for intracranial metastases of non-small-cell lung cancer (NSCLC; 25 patients with 32 lesions) and breast cancer (8 patients with 8 lesions). FGKS was performed in 3-5 fractions. Baseline MRI was performed before the first fraction. MRI was repeated after 1 or 2 fractions. Adaptive planning was executed based on new images. The median prescription dose was 8 Gy (range 6-10 Gy) with a 50% isodose line. On follow-up MRI, 18 of 40 lesions (45.0%) showed decreased tumor volumes (TVs). A significant difference was observed between baseline (median 15.8 cm3) and follow-up (median 14.2 cm3) volumes (p < 0.001). A conformity index was significantly decreased when it was assumed that adaptive planning was not implemented, from baseline (mean 0.96) to follow-up (mean 0.90, p < 0.001). The average reduction rate was 1.5% per day. The median follow-up duration was 29.5 weeks (range 9-94 weeks). During the follow-up period, local recurrence occurred in 5 lesions. The TV showed changes with a high dose of radiation during the course of FGKS. Volumetric change caused a significant difference in the clinical parameters. It is expected that adaptive planning would be helpful in the case of radiosensitive tumors such as NSCLCs or breast cancer to ensure an adequate dose to the target area and reduce unnecessary exposure of normal tissue to radiation.

Efficacy of platelet-rich plasma for the treatment of interstitial supraspinatus lesions: A randomized, double-blinded, controlled trial: PRP for Interstitial Supraspinatus Lesions

Objectives To determine whether platelet rich plasma (PRP) infiltrations are superior to saline solution infiltrations (placebo), when injected under ultrasound guidance within isolated interstitial supraspinatus tears, at improving healing, pain and function. Methods In this single-centre, double-blinded, randomized control trial, 84 adults, diagnosed with symptomatic isolated interstitial tears of the supraspinatus, confirmed by their magnetic resonance arthrography (MRA) were randomized to PRP or saline injections. Each patient received 2 injections at 1 month interval. The primary outcome was the change in lesion volume calculated on MRA, at 7months. The secondary outcomes were improvements in shoulder pain and clinical scores at &gt;12months. Results Pre-operative patient characteristics did not differ between the two groups. At 7 months, there were no significant differences between the PRP and control groups in terms of decrease in lesion size (-0.3±23.6mm3 vs -8.1±84.7mm3; p=0.18), reduction of pain on Visual Analogic Scale (2.3±3.0 vs 2±3.0; p=0.59), improvement of Single Assessment Numerical Evaluation (16.7±20 vs 14.2±29.0; p=0.65), Constant score (8.6±13.0 vs 10.6±19.0; p=0.60), or American Shoulder and Elbow Surgeons (19.5±20.0 vs 21.9±28.0; p=0.67) scores. Adverse effects (frozen shoulders and extension of lesion to bursal or articular surface) were significantly more frequent in the PRP group compared to the control group (54% vs 26%, p=0.02). Conclusion PRP injections within interstitial supraspinatus tears did not improve tendon healing nor clinical scores compared to saline injections, and were associated with more adverse events. These findings confirm that PRP is of little benefit in the treatment of rotator cuff tears.

Healing of Periapical Lesion in Teeth Obturated with Different Techniques and Lengths (Radiographic Assessment)

Aim: The purpose of this study was to assess healing of periapical lesion in either symptomatic or asymptomatic cases after obturation with different obturation techniques: cold lateral compaction and single cone obturation techniques at different apical extensions; 1 mm &2mm. Materials and Methods: A total of eighty patients were divided into two main groups; symptomatic or asymptomatic (n=40) then each group was subdivided into two subgroups (n=20) according to the obturation technique; subgroup a: Cold lateral compaction technique and subgroup b: single cone obturation technique. Further, each subgroup was divided into two divisions (n=10) depending on whether the apical extent; 1 or 2 mm from radiographic apex. All cases were prepared and obturated. CBCT scans were taken preoperatively, at 3, 6, and nine months and volume of the lesion was calculated to determine the treatment outcome. Data were then gathered, tabulated and statistically analyzed. Results: At 1mm, no significant difference between mean % changes in lesion volume after using lateral compaction or single cone techniques either asymptomatic or symptomatic along the evaluation periods while at 2mm lateral compaction technique showed higher mean % decrease in lesion volume than single cone technique after 3, 6 as well as 9 months. In both groups, using lateral compaction technique, no significant difference was recorded at 1 or 2 mm apical extension of filling while in single cone, at 1mm apical extension revealed higher decrease in lesion volume than 2mm Conclusions: Radiographic success rate of the single cone obturation technique was comparable with those of the lateral compaction obturation technique in root canal treatment of teeth with periapical lesions in short term evaluations at 1mm apical extension.

A Serial 10-Year Follow-Up Study of Atrophied Brain Lesion Volume and Disability Progression in Patients with Relapsing-Remitting MS.

Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (n = 76) and confirmed disability progression (n = 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression. The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54, P = .004) and remained significant across all time points (P ≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (R 2 = 0.27, R 2 change 0.11, P = .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23, P = .04) and 0-12 months (hazard ratio = 2.41, P = .022) was the only significant MR imaging predictor of time to confirmed disability progression. Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.

In Vitro Red Fluorescence as an Indicator of Caries Lesion Activity.

This in vitro study examined the utility of comparing red fluorescence between active and inactive caries lesions and investigated whether changes in red fluorescence and fluorescence loss are influenced by lesion activity following remineralization. Sixty-two noncavitated smooth surface caries lesions on extracted human teeth were classified into active or inactive lesions using the Nyvad system prior to a 12-day pH-cycling procedure. Quantitative light-induced fluorescence-digital images were used to measure fluorescence parameters before and after pH cycling. At baseline, the intensity (ΔR) and area (AΔR) of red fluorescence were 1.5- and 2.2-fold higher in active lesions than in inactive lesions (p<0.05). The ratio of AΔR to lesion area was associated with classification of active lesions (odds ratio = 1.031; 95% confidence interval = 1.005-1.058). After pH cycling, the active lesions showed about 2- and 8-fold greater reductions in the median values of AΔR and fluorescence loss related to lesion volume (ΔQ) compared with inactive lesions (p<0.05). In conclusion, red fluorescence differs depending on lesion activity, and the red fluorescence area and lesion volume change following remineralization. The results suggest that measuring red fluorescence may be a useful way of objectively evaluating lesion activity of smooth surface lesions.

Relationship between serum markers and volume of liver metastases in castration-resistant prostate cancer

BackgroundProstate cancer patients with liver metastases have a poor prognosis. To date, no study exists investigating the relationship between liver tumor burden and clinical laboratory markers. Materials and MethodsMetastatic castrate-resistant prostate cancer (mCRPC) patients with radiographic evidence of liver metastases were selected for this study. Volumetric measurements of liver metastases were ascertained for all available patients. Prostate specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), total bilirubin and hemoglobin (HGB) levels were then assessed to coincide with the scan dates. Univariate and multivariate mixed-model regression analysis were performed to evaluate the relationship between laboratory markers and liver lesion volume. Data sets with non-normal distribution were logarithmically transformed. Akaike information criteria (AIC) was used to identify the most reliable multivariate model. ResultsIn our heavily pretreated liver-metastatic patient population, univariate analysis demonstrated a statistically significant positive correlation between PSA (p = 0.0002), ALP (p = 0.0305), AST (p < 0.0001), ALT (p = 0.0049), and LDH (p = 0.0019) and liver lesion volume. Additionally, ALB (p = 0.0006) and HGB (p = 0.0103) had statistically significant negative correlation. Multivariate analysis identified AST and hemoglobin assessments as the best predictors of increasing liver lesion burden. Preliminary data on circulating tumor DNA (ctDNA) mutational and amplification findings are also reported. ConclusionsAnalysis identified AST and hemoglobin as optimal predictors of liver lesion volume. These patients have a heavy burden of ctDNA abnormalities. Further studies with a larger patient population are needed to verify these results.Micro Abstract: This study investigates the association between liver lesion burden and clinical laboratory markers in castrate-resistant prostate cancer patients with hepatic metastases. Our univariate analysis identified multiple laboratory markers as significant indicators of worsening hepatic disease. Multivariate analysis demonstrated that AST and hemoglobin were the most effective predictors of change in liver lesion volume.

Exploring individual multiple sclerosis lesion volume change over time: Development of an algorithm for the analyses of longitudinal quantitative MRI measures.

BackgroundMagnetic resonance imaging (MRI) is used to follow-up multiple sclerosis (MS) and evaluate disease progression and therapy response via lesion quantification. However, there is a lack of automated post-processing techniques to quantify individual MS lesion change.ObjectiveThe present study developed a secondary post-processing algorithm for MS lesion segmentation routine to quantify individual changes in volume over time.MethodsAn Automatic Follow-up of Individual Lesions (AFIL) algorithm was developed to process time series of pre-segmented binary lesion masks. The resulting consistently labelled lesion masks allowed for the evaluation of individual lesion volumes. Algorithm performance testing was executed in seven early MS patients with four MRI visits, and MS experienced readers verified the accuracy.ResultsAFIL distinguished 328 individual MS lesions with a 0.9% error rate to track persistent or new lesions based on expert assessment. A total of 121 new lesions evolved within the observed time period. The proportional courses of 69.1% lesions in the persistent lesion population exhibited varying volume, 16.9% exhibited stable volume, 3.4% exhibiting continuously increasing, and 0.5% exhibited continuously decreasing volume.ConclusionThis algorithm tracked individual lesions to automatically create an individual lesion growth profile of MS patients. This approach may allow for characterization of patients based on their individual lesion progression.

Pretreatment texture analysis of routine MR images and shape analysis of the diffusion tensor for prediction of volumetric response after radiosurgery for meningioma.

OBJECTIVEThe goal of this study was to identify parameters from routine T1- and T2-weighted MR sequences and diffusion tensor imaging (DTI) that best predict the volumetric changes in a meningioma after treatment with Gamma Knife radiosurgery (GKRS).METHODSIn 32 patients with meningioma, routine MRI and DTI data were measured before GKRS. A total of 78 parameters derived from first-level texture analysis of the pretreatment MR images, including calculation of the mean, SD, 2.5th and 97.5th percentiles, and kurtosis and skewness of data in histograms on a voxel-wise basis, were correlated with lesion volume change after a mean follow-up period of 3 years (range 19.5-63.3 months).RESULTSSeveral DTI-derived parameters correlated significantly with a meningioma volume change. The parameter that best predicted the results of GKRS was the 2.5th percentile value of the smallest eigenvalue (L3) of the diffusion tensor (correlation coefficient 0.739, p ≤ 0.001), whereas among the non-DTI parameters, only the SD of T2-weighted images correlated significantly with a tumor volume change (correlation coefficient 0.505, p ≤ 0.05, after correction for family-wise errors using false-detection-rate correction).CONCLUSIONSDTI-derived data had a higher correlation to shrinkage of meningioma volume after GKRS than data from T1- and T2-weighted image sequences. However, if only routine MR images are available, the SD of T2-weighted images can be used to predict control or possible progression of a meningioma after GKRS.

Long‐term, single‐arm, open‐label, multicenter phase 2/4 study of glatiramer acetate by subcutaneous injection in Japanese patients with relapsing–remitting multiple sclerosis

AbstractObjectiveGlatiramer acetate (GA) has been shown to be a well‐tolerated and effective treatment for patients with multiple sclerosis (MS) with relapse. The present open‐label study aimed to evaluate the efficacy and safety of long‐term treatment with GA.MethodsJapanese patients with relapsing–remitting MS received up to 52‐weeks’ treatment with GA 20 mg/mL once daily in the phase 2 study. In phase 4, patients continued to receive treatment after marketing approval in Japan until commercial availability. Key end‐points were safety and tolerability of GA. Other analyses included numbers and volumes of gadolinium‐enhancing and T2‐weighted (T2) lesions.ResultsOf 17 patients initially treated, 13 completed 52 weeks’ therapy and 10 completed the phase 4 extension (efficacy assessment: 104 weeks; maximum treatment period/long‐term safety assessment: up to 5 years). No new safety signals were observed; most adverse events were mild or moderate, with injection site reactions being the most common. The number of T1 gadolinium‐enhancing lesions declined from 2.9 (baseline) to 1.3 (week 104), and the number of T2 lesions increased from 1.7 to 6.7. T1 and T2 lesion volume changes were not clinically meaningful (changes of −0.090 and 0.088 mL, respectively, by week 104). The mean annualized relapse rate was 2.01 (baseline) and 1.78 (week 104); the mean Expanded Disability Status Scale scores indicated reduced levels of disability.ConclusionsThese findings suggest the favorable tolerability and safety profile of GA in Japanese patients, and provide supportive evidence for the efficacy of GA in reducing MS recurrence and improving disability in Japanese MS patients.

Repeatability of dynamic contrast enhanced vp parameter in healthy subjects and patients with brain tumors.

To study the repeatability of plasma volume (vp) extracted from dynamic-contrast-enhanced (DCE) MRI in order to define threshold values for significant longitudinal changes, and to assess changes in patients with high-grade-glioma (HGG). Twenty eight healthy subjects, of which eleven scanned twice, were used to assess the repeatability of vp within the normal-appearing brain tissue and to define threshold values for significant changes based on least-detected-differences (LDD) of mean vp values and histogram comparisons using earth-mover's-distance (EMD). Sixteen patients with HGG were scanned longitudinally with eight patients scanned before and following bevacizumab therapy. Longitudinal changes were assessed based on defined threshold values in comparison to RANO criteria. The threshold values for significant changes were: LDD = 0.0024 (ml/100ml, 21%) for mean vp and EMD = 4.14. In patients, in 20/24 comparisons, no significant longitudinal changes were detected for vp within the normal-appearing brain tissue. Concurring results were obtained between changes in lesion volume (RANO criteria) and LDD or EMD values in cases diagnosed with progressive-disease, yet in about 50% of cases diagnosed with partial-response preliminary results demonstrated significant increase in vp despite significant reductions in lesion volume. In two patients, these changes preceded progression detected at follow-up scans. In general, a good concordance was obtained between LDD and EMD. This study shows high repeatability of vp and provides threshold values for significant changes in longitudinal assessment of patients with brain tumors. Preliminary results suggest the use of vp-DCE parameter to improve assessment of therapy response in patients with high-grade-glioma.

Optimized Feature Extraction for Radiomics Analysis of 18F-FDG PET Imaging.

Radiomics analysis of 18F-FDG PET/CT images promises well for an improved in vivo disease characterization. To date, several studies have reported significant variations in textural features due to differences in patient preparation, imaging protocols, lesion delineation, and feature extraction. Our objective was to study variations in features before a radiomics analysis of 18F-FDG PET data and to identify those feature extraction and imaging protocol parameters that minimize radiomic feature variations across PET imaging systems. Methods: A whole-body National Electrical Manufacturers Association image-quality phantom was imaged with 13 PET/CT systems at 12 different sites following local protocols. We selected 37 radiomic features related to the 4 largest spheres (17-37 mm) in the phantom. On the basis of a combined analysis of voxel size, bin size, and lesion volume changes, feature and imaging system ranks were established. A 1-way ANOVA was performed over voxel size, bin size, and lesion volume subgroups to identify the dependency and the trend change in feature variations across these parameters. Results: Feature ranking revealed that the gray-level cooccurrence matrix and shape features are the least sensitive to PET imaging system variations. Imaging system ranking illustrated that the use of point-spread function, small voxel sizes, and narrow gaussian postfiltering helped minimize feature variations. ANOVA subgroup analysis indicated that variations in each of the 37 features and for a given voxel size and bin size can be minimized. Conclusion: Our results provide guidance to selecting optimized features from 18F-FDG PET/CT studies. We were able to demonstrate that feature variations can be minimized for selected image parameters and imaging systems. These results can help imaging specialists and feature engineers in increasing the quality of future radiomics studies involving PET/CT.

Pretreatment Texture Analysis of Routine Magnetic Resonance Images and Shape Analysis of the Diffusion Tensor Predict Volumetric Response after Radiosurgery for Meningiomas

Tumor progression after stereotactic radiosurgery remains a major complication in WHO grade I meningiomas, with figures reported between 5-10%. According to our previous study, Diffusion Tensor Imaging (DTI) parameters can differentiate between meningioma subtypes and predict the reduction in volume of meningiomas after SRS. However DTI is still not frequently performed for SRS. The objective of this study was to identify those parameters from routine T1- and T2-weigted Magnetic Resonance (MR) sequences, and as well as from DTI, which predict best volume changes of meningiomas after Gamma Knife Radio-Surgery (GKRS) treatment. In 32 patients (mean age 58y) with meningiomas (mean volume 8.80cm3, mean dose 14.2Gy), routine 3 Tesla MR images as well as 11 different DTI parameter maps, including skewness of tensor shape, were measured before SRS. A total of 104 parameters derived from first level texture analysis of the pre-treatment MR images, including calculation of mean, standard deviation, 2.5 and 97.5 percentiles, kurtosis and skewness of data histograms on a voxel-wise basis, were correlated with lesion volume change after a mean follow up period of 3 years (19.5 – 63.3 months). Mean volume change rate per month after SRS was 0.92%. 1 (3%) meningioma progressed, 5 (16%) meningiomas stayed stable and 26 (81%) regressed. Several DTI-derived parameters correlated significantly with meningioma volume change. The parameter to predict best response of SRS was the 2.5 percentile value of the planar spherical index of the diffusion tensor (correlation coefficient -0.682, p≤0.001), whereas from the non-DTI parameters, only standard deviation of T2-weighted data correlated significantly with tumor volume change (correlation coefficient 0.505, p≤0.05). Other factors, like original tumor size, prescription dose and patient’s age, did not present significant correlation. WHO grade I Meningiomas differ in tissue homogeneity and in radiosensitivity. DTI-derived parameters show a higher correlation to shrinkage of meningioma volume after SRS than data from T1- and T2-weigted sequences. Combinations of standard deviation of T2 and DTI parameters can further improve correlation. If only routine MR images are available, standard deviation of T2-weighted images may be considered to predict volumetric response of meningiomas after SRS.

Non-invasive monitoring of longitudinal changes in cerebral hemodynamics in acute ischemic stroke using BOLD signal delay

Relative delays in blood-oxygen-level-dependent (BOLD) signal oscillations can be used to assess cerebral perfusion without using contrast agents. However, little is currently known about the utility of this method in detecting clinically relevant perfusion changes over time. We investigated the relationship between longitudinal BOLD delay changes, vessel recanalization, and reperfusion in 15 acute stroke patients with vessel occlusion examined within 24 h of symptom onset (D0) and one day later (D1). We created BOLD delay maps using time shift analysis of resting-state functional MRI data and quantified perfusion lesion volume changes (using the D1/D0 volume ratio) and severity changes (using a linear mixed model) over time. Between baseline and follow-up, BOLD delay lesions shrank (median D1/D0 ratio = 0.2, IQR = 0.03–0.7) and BOLD delay severity decreased (b = −4.4 s) in patients with recanalization, whereas they grew (median D1/D0 ratio = 1.47, IQR = 1.1–1.7) and became more severe (b = 4.3 s) in patients with persistent vessel occlusion. Clinically relevant changes in cerebral perfusion in early stroke can be detected using BOLD delay, making this non-invasive method a promising option for detecting tissue at risk of infarction and monitoring stroke patients following recanalization therapy.

Monitoring optic chiasmatic-hypothalamic glioma volumetric changes by MRI in children under clinical surveillance or chemotherapy.

Optic pathway gliomas represent 5% of pediatric brain tumors and are typically low-grade lesions. Because of their unpredictable clinical course, adequate treatment approaches have been controversial, involving surveillance, surgery, chemotherapy, and radiotherapy. In this study, we use volumetric imaging to compare evolution of optic chiasmatic-hypothalamic gliomas (OCHG) treated with and without chemotherapy, analyzing tumor volume variation during the overall period. A total of 45 brain MRI were retrospectively analyzed for 14 patients with OCHG. Volumetric assessment of the lesions was performed by a neuroradiologist, using software DISPLAY. OCHG patients were allocated into two groups: group 1 (n = 8) who underwent chemotherapy and group 2 (n = 6) who did not receive chemotherapy. Outcome analysis was performed comparing tumor volume evolution of these two groups. The results showed a reduction of 4.4% of the volume of the lesions for group 1 after the end of chemotherapy, with an increase of 5.3% in volume in the late follow-up examination. For group 2, we found a slight reduction (5%) of the overall volume of the lesions, both with no statistical significance (p > 0.05). From the limited series analyzed in this study, no significant differences were observed in relation to the volume change of lesions treated or not treated with chemotherapy. Larger prospective clinical trials are needed to better evaluate the effect of chemotherapy and radiological response of OCHG.

A longitudinal magnetic resonance imaging study of neurodegenerative and small vessel disease, and clinical cognitive trajectories in non demented patients with transient ischemic attack: the PREVENT study

BackgroundLate-life cognitive decline, caused by progressive neuronal loss leading to brain atrophy years before symptoms are detected, is expected to double in Canada over the next two decades. Cognitive impairment in late life is attributed to vascular and lifestyle related risk factors in mid-life in a substantial proportion of cases (50%), thereby providing an opportunity for effective prevention of cognitive decline if incipient disease is detected earlier. Patients presenting with transient ischemic attack (TIA) commonly display some degree of cognitive impairment and are at a 4-fold increased risk of dementia. In the Predementia Neuroimaging of Transient Ischemic Attack (PREVENT) study, we will address what disease processes (i.e., Alzheimer’s vs. vascular disease) lead to neurodegeneration, brain atrophy, and cognitive decline, and whether imaging measurements of brain iron accumulation using quantitative susceptibility mapping predicts subsequent brain atrophy and cognitive decline.MethodsA total of 440 subjects will be recruited for this study with 220 healthy subjects and 220 TIA patients. Early Alzheimer’s pathology will be determined by cerebrospinal fluid samples (including tau, a marker of neuronal injury, and amyloid β1–42) and by MR measurements of iron accumulation, a marker for Alzheimer’s-related neurodegeneration. Small vessel disease will be identified by changes in white matter lesion volume. Predictors of advanced rates of cerebral and hippocampal atrophy at 1 and 3 years will include in vivo Alzheimer’s disease pathology markers, and MRI measurements of brain iron accumulation and small vessel disease. Clinical and cognitive function will be assessed annually post-baseline for a period of 5-years using a clinical questionnaire and a battery of neuropsychological tests, respectively.DiscussionThe PREVENT study expects to demonstrate that TIA patients have increased early progressive rates of cerebral brain atrophy after TIA, before cognitive decline can be clinically detected. By developing and optimizing high-level machine learning models based on clinical data, image-based (quantitative susceptibility mapping, regional brain, and white matter lesion volumes) features, and cerebrospinal fluid biomarkers, PREVENT will provide a timely opportunity to identify individuals at greatest risk of late-life cognitive decline early in the course of disease, supporting future therapeutic strategies for the promotion of healthy aging.

Achillea millefolium is beneficial as an add-on therapy in patients with multiple sclerosis: A randomized placebo-controlled clinical trial

BackgroundMultiple sclerosis (MS) is a neurological disease for which to date there is no cure and the existing disease-modifying drugs just slow down the disease progression. PurposeIn this clinical trial we evaluated the efficacy of Achillea millefolium (A. millefolium) aqueous extract in MS patients. MethodsA triple-blind randomized placebo-controlled parallel group trial was conducted on 75 MS patients. The patients were randomized into three groups including placebo and two groups receiving A. millefolium with two different doses, i.e. 250 mg/day and 500 mg/day, for 1 year. The primary outcome was the annualized relapse rate. Also, number and volume of lesions were obtained from magnetic resonance imaging (MRI) scans. Furthermore, we performed a comprehensive neurological and cognitive tests as follows: changes in the expanded disability status scale (EDSS), the multiple sclerosis functional composite (MSFC), fatigue severity scale (FSS), Ashworth spasticity assessment, Beck depression test, State-trait anxiety inventory (STAI), mini-mental status examination (MMSE), Wisconsin card sorting test (WCST), tower of London test (TOL), word-pair learning, paced auditory serial addition task (PASAT) and standard laboratory tests. ResultsThis study showed one year administration of A. millefolium (both doses) decreased the annual relapse rate in MS patients. The mean volume change of lesions significantly decreased in the 500 mg A. millefolium group. The add-on therapy also increased time to first relapse and the MSFC z-score; it decreased the EDSS score and improved performance in word-pair learning, PASAT, and WCST. ConclusionWe found beneficial effects of A. millefolium aqueous extract as an add-on therapy in MS patients.

Abstract TP47: Prediction of Stroke Outcome With Immediate Post-Thrombolysis Magnetic Resonance Imaging

Background: Early recanalization and adequate collateral blood flow are strong surrogates for functional recovery in endovascular stroke treatment. We sought to evaluate the prognostic value of immediate post-thrombolysis magnetic resonance imaging (MRI). Methods: Consecutive patients with acute ischemic stroke who underwent endovascular treatment were enrolled. We measured diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) lesion volume, mismatch ratio, and DWI and PWI lesion volume change before and immediate after treatment. Outcome was measured with modified Rankin Scale (mRS) at 90 days, early neurological improvement (NIHSS ≥ 8) within 7 days, and any intracerebral hemorrhage. Multivariate analysis and c -statistics were used to identify prognostic value of MR parameters. Results: A total of 65 patients with a complete pre- and post-thrombolysis MRI were included. Mean age was 65±18 years, median baseline NIHSS score was 14, and median time from symptom onset to endovascular treatment was 192 minutes. Median time from endovascular treatment to post-treatment MRI was 20 minutes. After control of initial stroke severity and complete recanalization on angiography, post-thrombolysis PWI lesion volume remained an independent predictor of favorable outcome ( p = 0.017, odds ratio [OR] = 0.970, 95% confidence interval [CI] = 0.946-0.995), and early neurological improvement ( p = 0.014, OR = 0.957, 95% CI = 0.923-0.991), whereas DWI lesion volume, mismatch ratio, and DWI and PWI lesion volume changes did not show statistical significance. None of the measured variables predicts intracerebral hemorrhage. Post-thrombolysis PWI lesion volume revealed area under the curve of 0.821 (p &lt; 0.001, 95% CI = 0.722-0.920) for favorable outcome and 0.878 (p &lt; 0.001, 95% CI = 0.799-0.957) for early neurological improvement. Conclusions: Perfusion lesion volume on immediate post-thrombolysis MRI more accurately predicts functional recovery and early neurological improvement than pre-treatment DWI and PWI parameters.

Validating Nonlinear Registration to Improve Subtraction Images for Lesion Detection and Quantification in Multiple Sclerosis.

To propose and validate nonlinear registration techniques for generating subtraction images because of their ability to reduce artifacts and improve lesion detection and lesion volume quantification. Postcontrast T1 -weighted spin echo and T2 -weighted dual echo images were acquired for 20 patients with relapsing-remitting multiple sclerosis (RRMS) on a monthly basis for a year (14 women, average age 33.6 ± 6.9). The T2 -weighted images from the first scan were used as a baseline for each patient. The images from the last scan were registered to the baseline image. Four different registration algorithms used for evaluation included; linear, halfway linear, nonlinear, and nonlinear halfway. Subtraction images were generated after brain extraction, intensity normalization, and Gaussian blurring. Lesion activity changes along with identified artifacts were scored on all four techniques by two independent observers. Additionally, quantitative analysis of the algorithms was performed by estimating the volume changes of simulated lesions and real lesions. For real lesion volume change analysis, five subjects were selected randomly. Subtraction images were generated between all the 11 time points and the baseline image using linear and nonlinear registration for the five subjects. Lesion activity detection resulted in similar performance among the four registration techniques. Lesion volume measurements on subtraction images using nonlinear registration were closer to lesion volume on T2 -weighted images. A statistically significant difference was observed among the four registration techniques while evaluating yin-yang artifacts. Pairwise comparisons showed that nonlinear registration results in the least amount of yin-yang artifacts, which are significantly different. Nonlinear registration for generation of subtraction images has been demonstrated to be a promising new technique as it shows improvement in lesion activity change detection. This approach decreases the number of artifacts in subtraction images. With improved lesion volume estimates and reduced artifacts, nonlinear registration may lead to discarding less subject data and an improvement in the statistical power of subtraction imaging studies.

Diffusion-Weighted MRI Stroke Volume Following Recanalization Treatment is Threshold-Dependent.

Infarct lesion segmentation has been problematic as there are awide range of relative and absolute diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) thresholds that have been used for this purpose. We examined differences of stroke lesion volume and evolution evaluated by magnetic resonance imaging (MRI) during the immediate post-treatment phase (<5 h) and at 24 h. In this study 33acute ischemic stroke patients were imaged with MRI <5 h and 24 h post-reperfusion treatment. Lesion volumes were segmented on ADC maps and average DWI using literature cited absolute ADC and relative DWI thresholds. The segmented lesion volumes within both time points were compared and the absolute change in lesion volume (infarct growth) between the two time points was calculated and compared using Bland-Altman analysis. Lesion volumes differed significantly when different relative DWI or absolute ADC thresholds were used (p< 0.05), which held true for baseline as well as follow-up lesions. The median absolute changes in lesion volume from baseline to follow-up for ADC thresholds of 550× 10-6 mm2/s, 600× 10-6 mm2/s, 630× 10-6 mm2/s and 650× 10-6 mm2/s were 3.5 ml, 4.2 ml, 4.5 ml, and 6.5 ml, respectively (p< 0.05). Likewise, the median absolute changes in lesion volume from baseline to follow-up for DWI thresholds, k= 0.85, 1.28, 1.64, 1.96, and 2.7 were 10.1ml, 7.3 ml, 5.7 ml, 5.4 ml and 4.2 ml, respectively (p< 0.05). Absolute lesion volumes and changes in lesion volumes (infarct growth) measured after recanalization treatment were dependent on absolute ADC and relative DWI thresholds, which may have clinical significance. Standardization of techniques for measuring DWI lesion volumes requires immediate attention.