Radiographic Surrogate Research Articles

The subcoracoid distance is correlated with pain and internal rotation after reverse shoulder arthroplasty

A proposed etiology of anterior shoulder pain and limited internal rotation after reverse shoulder arthroplasty (RSA) is impingement of the humeral component on the coracoid or conjoint tendon. The primary goal of this study was to investigate radiographic surrogates for potential coracoid or conjoint tendon impingement and their relationship to postoperative pain and internal rotation after RSA. A retrospective review of a clinical registry was performed to identify patients with (1) primary RSA, (2) minimum 2-year clinical follow-up, and (3) satisfactory postoperative axillary lateral radiographs. The primary radiographic measurement of interest was the subcoracoid distance (SCD), defined as the distance between the posterior aspect of the coracoid and the anterior glenosphere. Additional measurements were as follows: anterior glenosphere overhang, posterior glenosphere overhang, native glenoid width, lateralization of glenosphere relative to the coracoid tip, lateralization shoulder angle, and distalization shoulder angle. The primary clinical outcome of interest was the 2-year postoperative Visual Analog Scale score. Secondary outcomes were (1) internal rotation (IR) defined by spinal level (IRspine), (2) IR at 90 degrees of abduction, (3) American Shoulder and Elbow Surgeons score, (4) forward flexion, and (5) external rotation at 0 degrees of abduction. Linear regression analyses were used to evaluate the relationship of the various radiographic measures on the clinical outcomes of interest. Two hundred seventeen patients were included. There was a statistically significant relationship between the SCD and Visual Analog Scale scores: B=-0.497, P=.047. There was a statistically significant relationship between the SCD and IRspine: B=-1.667, P<.001. Metallic lateralization was also positively associated with improving IRspine; increasing body mass index was negatively associated. There was a statistically significant relationship between the SCD and IR at 90 degrees of abduction: B=5.844, P=.034. For RSA with a 135° neck shaft angle and lateralized glenoid, the postoperative SCD has a significant association with pain and IR. Decreasing SCD was associated with increased pain and decreased IR, indicating that coracoid or conjoint tendon impingement may be an important and potentially under-recognized etiology of pain and decreased IR following RSA. Further investigations aimed toward identifying a critical SCD to improve pain and IR may allow surgeons to preoperatively plan component position to improve clinical outcomes after RSA.

Sedation protocols in non-traumatic SAH (SPRINT-SAH): A cross-sectional survey among German-speaking neurointensivists.

In subarachnoid hemorrhage (SAH), titrating sedation to find a balance between wakefulness with the ability to perform valid clinical examinations on the one hand, and deep sedation to minimize secondary brain damage, on the other hand, is challenging. However, data on this topic are scarce, and current guidelines do not provide recommendations for sedation protocols in SAH. We designed a web-based, cross-sectional survey for German-speaking neurointensivists to map current standards for the indication and monitoring of sedation, duration of prolonged sedation, and biomarkers for the withdrawal of sedation. Overall, 17.4% (37/213) of neurointensivists answered the questionnaire. Most of the participants were neurologists (54.1%, 20/37) and exhibited a long-standing experience in intensive care medicine (14.9 years, SD 8.3). Among indications for prolonged sedation in SAH, the control of intracranial pressure (ICP) (94.6%) and status epilepticus (91.9%) were most significant. With regard to further complications in the course of the disease, therapy refractory ICP (45.9%, 17/37) and radiographic surrogates of elevated ICP, such as parenchymal swelling (35.1%, 13/37), were the most relevant topics for experts. Regular awakening trials were performed by 62.2% of neurointensivists (23/37). All participants used clinical examination for the therapeutic monitoring of sedation depth. A total of 83.8% of neurointensivists (31/37) used methods based on electroencephalography. As a mean duration of sedation before attempting an awakening trial in patients with unfavorable biomarkers, neurointensivists suggested 4.5 days (SD 1.8) for good-grade SAH and 5.6 days (SD 2.8) for poor-grade SAH, respectively. Many experts performed cranial imaging before the definite withdrawal of sedation [84.6% (22/26)], and 63.6% (14/22) of the participants required an absence of herniation, space-occupying lesions, or global cerebral edema. The values of ICP tolerated for definite withdrawal were smaller compared to that of awakening trials (17.3 mmHg vs. 22.1 mmHg), and patients were required to stay below the threshold value for several hours (21.3 h, SD 10.7). Despite the paucity of clear recommendations for sedation management in SAH in the pre-existing literature, we found some level of agreement indicating clinical efficacy for certain clinical practices. By mapping the current standard, this survey may help to identify controversial aspects in the clinical care of SAH and thereby streamline future research.

Sarcopenia as a Predictor of Survival in Patients with Pancreatic Adenocarcinoma After Pancreatectomy.

To determine whether sarcopenia can potentially predict worse survival after resection of pancreatic ductal adenocarcinoma. Sarcopenia is correlated with poor outcomes in hepatopancreatobiliary malignancies, but the relationship of both its qualitative and quantitative features with patient survival after pancreatectomy has not been investigated in a western population. Preoperative cross-sectional computed tomography scans of consecutive patients who underwent pancreatectomy in 2005-2017 were evaluated for skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific categorical cut-offs were determined. Findings were correlated with outcome. The study included 111 patients, 47% of whom were female, with a median age of 67 years (range: 35-87 years), and median body mass index of 23kg/m2 (range: 16-40kg/m2); 77% had a Whipple procedure and 66% received adjuvant chemotherapy. Low SMI correlated with poor overall survival (OS) (P = 0.007), disease-specific survival (DSS) (P = 0.006), and recurrence-free survival (RFS) (P = 0.01). High IMAC correlated with poor OS (P = 0.04). Patients with high IMAC tended to have a shorter DSS (P = 0.09), with no correlation with RFS (P = 0.6). VSR was not associated with survival. Multivariable analysis yielded an independent association of low SMI with OS (HR = 1.7, 95%CI: 1.1-2.8, P = 0.02), DSS (HR = 1.8, 95%CI:1.03-3.2, P = 0.04), and RFS (HR = 1.8, 95%CI: 1.1-2.8, P = 0.01), and of high IMAC with OS (HR = 1.9, 95%CI: 1.1-3.1, P = 0.01). Both qualitative and quantitative measures of skeletal muscle were independently associated with impaired survival in patients with resectable PDAC. Sarcopenia might serve as an early radiographic surrogate of aggressive tumor behavior, with potential implications for clinical decision-making and future study.

The assessment of sarcopenia using psoas muscle thickness per height is not predictive of post-operative complications in IBD

Background Sarcopenia is associated with postoperative complications in inflammatory bowel disease. It has most commonly been defined using the skeletal muscle index, computed after analysis of cross-sectional muscle area at L3. Psoas muscle thickness normalized to height (PMTH), which is easier to derive, is a potential surrogate of SMI and sarcopenia in patients with cirrhosis and chronic pancreatitis. We investigate whether sarcopenia defined by PMTH has utility in predicting post-operative outcomes in patients with inflammatory bowel disease. Methods We performed a retrospective study of adults undergoing IBD-related surgery from 2009 to 2019 at two hospitals. Sarcopenia was defined by sex-specific PMTH at the umbilicus on cross-sectional imaging using a 50th percentile median cutoff. Predictive models were created using variables (BMI, age, sex, smoking status, albumin, INR, platelets, hemoglobin, hypertension, diabetes, CAD, medications) that may be associated with complications (mortality, reoperation, readmission, transfusions, ICU admission, infection, DVT/PE), and sarcopenia for comparison. Results 85 patients with IBD were included. Lower albumin level (OR = 0.52, p = 0.039) and biologic use (OR = 5.92, p = 0.006) were associated with postoperative complications. There was no significant difference using PMTH compared to a model incorporating hypoalbuminemia and biologic use in predicting complications. Sarcopenia on univariate analysis was associated with a lower 30 day rate of reoperation (p = 0.04). Conclusions A low status of PMTH was not associated with increased postoperative complications, however hypoalbuminemia and biologic use were. PMTH as a surrogate for sarcopenia requires further study, ideally with prospective studies comparing PMTH with accepted radiographic surrogates for sarcopenia, to determine its role in clinical decision making.

Can we rely on surgical clips placed during oncoplastic breast surgery to accurately delineate the tumor bedfor targeted breast radiotherapy?

Oncoplastic breast surgery (OBS) is gaining popularity among surgeons for breast-conserving surgery treatments. OBS relies on complex relocation and deformation of breast tissue involving the tumor bed (TB). In this study, we investigate the validity of using surgical clips with OBS for accurate TB delineation in adjuvant, targeted breastradiotherapy. Different OBS techniques were simulated on realistic breast phantoms. Surgical clips were used to demarcate the TB. Following tumor resection and closure, the true TB (TBTrue) was extracted. Each phantom was CT imaged at several phases of surgery in order to record pre- and post-OBS closure surgical clip displacements. Two senior radiation oncologists (ROs) were asked to delineate TBs on CTs by relying on surgical clips placedas per standard protocol, and by referring to operative notes. Their original contours, as well as those expanded using 5-15 mm margins, were compared with the accurate TBTrue using the dice similarity coefficient (DSC), Hausdorff Distance (HD), and over- and under-contoured volumes. Inter- and intra-RO contour agreements were also evaluated. Post-OBS surgical clips were significantly displaced outside the original breast quadrant. Inter- and Intra-RO TB contours were consistent, yet systematically differed from TBTrue (DSC values range = 0.38 to 0.69, and maximum HD range = 17.8 mm to 38.0mm). Using expansion margins did not improve contour congruence and caused significant over-contoured volumes. Following OBS, surgical clips alone are not reliable radiographic surrogates of TB locations and accurate TB delineation is challenging. For complex OBS cases, indication of any type of partial breast irradiation is very questionable.

P017 Sarcopenia Defined by Psoas Muscle Thickness is Not a Predictor of Post-Operative Outcomes in IBD Patients.

BACKGROUND: Sarcopenia, or muscle mass loss, has been associated with post-operative complications in inflammatory bowel disease (IBD). It is commonly diagnosed by skeletal muscle index (SMI), which is computed by specialized software using several cross-sectional muscle areas at the L3 vertebral body level and is labor intensive. In contrast, psoas muscle thickness normalized to height (PMTH) is calculated quickly without specific software and has potential for routine community use. PMTH is a potential surrogate of SMI and sarcopenia in cirrhosis and chronic pancreatitis. Our aim was to investigate whether sarcopenia defined by PMTH has utility in a predictive model for post-operative complications in IBD. METHODS: We performed a retrospective study of adults undergoing IBD related surgical resections from 2009 to 2019 at two hospitals. Patients with MRI or CT scans within 90 days preoperatively to 7 days postoperatively were included. Sarcopenia was defined by sex-specific PMTH at the level of the umbilicus on MRI or CT images using a 50th percentile median cutoff (17.8 mm/m in males, 14.8 mm/m in females). Predictive models were created using variables (BMI, age, gender, smoking status, albumin level, INR, platelet count, hemoglobin level, hypertension, diabetes, coronary artery disease, steroid/immunomodulator/biologic use) associated with complications (defined as mortality within 30 days, reoperation within 30 days, readmission within 90 days, RBC transfusion, ICU admission, sepsis, any infection, or DVT/PE). Additional predictive models were created incorporating sarcopenia for comparison. P-values were obtained using univariate logistic regression with P < 0.05 significant. True area under the curve (AUC) was estimated to be within 0.7 to 0.9, with 0.8 as a cut point for clinical relevance. RESULTS: A total of 85 patients (66% Crohn's disease, 34% Ulcerative colitis, 48 male, 37 female) with mean age 42.5 ± 14.6 were included. Eighty-four patients were on at least one medication for IBD, including 52.4% on steroids, 23.8% on immunomodulators, and 23.8% on biologics. Albumin level (OR = 0.52, P = 0.039) and biologic use (OR = 5.92, P = 0.006) were significantly associated with post-operative complications. The predictive models incorporating sarcopenia, either as a dichotomous variable or PMTH as a continuous variable, were not significantly different from a model with hypoalbuminemia and biologic use (P = 0.73). Sarcopenia on univariate analysis was only significantly associated with lower rate of 30-day reoperation (P = 0.04). CONCLUSION: While PMTH as a surrogate marker for sarcopenia was not a predictor of post-operative outcomes, hypoalbuminemia and biologic use were. An unexpected association between sarcopenia and lower 30-day reoperation rates may be due to hesitancy to take sarcopenic patients back to the operating room. Sarcopenia defined by PMTH may have a role in decision making with nutritional markers, however larger studies that compare PMTH with accepted radiographic surrogates for sarcopenia and risk assessment in IBD patients are needed.

The quadriceps insertion of the medial patellofemoral complex demonstrates the greatest anisometry through flexion

A comprehensive understanding of the biomechanical properties of the medial patellofemoral complex (MPFC) is necessary when performing an MPFC reconstruction. How components of the MPFC change over the course of flexion can influence the surgeon's choice of location for graft fixation along the extensor mechanism. The purpose of this study was to (1) determine native MPFC length changes throughout a 90° arc using an anatomically based attachment and using Schöttle's point, and (2) compare native MPFC length changes with different MPFC attachment sites along the extensor mechanism. Eight fresh-frozen (n = 8), cadaveric knees were dissected of all soft tissue structures except the MPFC. The distance between the femoral footprint (identified through anatomical landmarks and Schottle's point) and the MPFC was calculated at four attachment sites along the extensor mechanism [midpoint of the patella [MP], the center of the osseous footprint of the MPFC (FC), the superomedial corner of the patella at the quadriceps insertion (SM), and the proximal extent of the MPFC along the quadriceps tendon (QT)] at 0°, 20°, 40°, 60°, and 90° of flexion. Length changes were investigated between the MPFL femoral attachment site and the radiographic surrogate of the MPFL attachment site, Schottle's Point (SP). Paired t tests at each of the four components showed no differences in length change from 0° to 90° when comparing SP to the anatomic MPFC insertion. MPFL length changes from 0° to 90° were greatest at the QT point (13.9 ± 3.0mm) and smallest at the MP point (2.7 ± 4.4mm). The FC and SM points had a length change of 6.6 ± 4.2 and 9.0 ± 3.8, respectively. Finally, when examining how the length of the MPFC components changed through flexion, the greatest differences were seen at QT where all comparisons were significant(p<0.01) except when comparing 0° vs 20° (n.s.). The MPFC demonstrates the most significant length changes between 0° and 20° of flexion, while more isometric behavior was seen during 20°-90°. The attachment points along the extensor mechanism demonstrate different length behaviors, where the more proximal components of the MPFC display greater anisometry through the arc of motion. When performing a proximal MPFC reconstruction, surgeons should expect increased length changes compared to reconstructions utilizing distal attachment sites.

Increased Cortical Glycolysis Following CD19 CART Therapy: A Radiographic Surrogate for an Altered Blood-Brain Barrier

Background: Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are known complications of chimeric antigen receptor T-cell (CAR-T) therapy. These clinical syndromes develop as a result of CAR-T activation, proliferation, and tumor lysis with resultant cytokine secretion. In prior reports of CD19 CAR-T therapy patients, those who developed ICANS showed evidence of endothelial activation and disruption of the blood-brain barrier as a result of cytokine release while only approximately one-third demonstrated changes on Brain MRI (Gust et al. Cancer Discov 2017). As such, further predictive markers and studies are needed to identify patients at risk for ICANS to allow for expedited management and improved outcomes. Herein we report a single-center analysis exploring glycolytic activity on PET/CT and the association with clinical outcomes for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) after CAR-T therapy. Methods: An organ-based evaluation of uninvolved sites was conducted in R/R DLBCL patients (n=32) who underwent CD19 CAR-T therapy with evaluable PET/CT imaging at baseline immediately prior to CAR-T therapy and at 30 days post-infusion (D+30). All patients in this analysis were treated with axicabtagene ciloleucel as standard of care therapy after 2 or more lines of therapy. Tumor metabolic volume (TMV) and mean standard uptake value (SUVmean) of various organs were quantified using ROVER [Region of interest (ROI) visualization, evolution, and image registration] software (ABX advanced biochemical compounds GmbH, Radeberg, Germany). Statistical analysis was completed using STATA 14 (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP). All tests were performed after testing the normality distribution assumption. Temporal changes were assessed using paired t-tests, and between-group analyses were completed with two-sample t-tests. Results: SUVmean increased significantly after CAR-T therapy in the following organs (D+30 v baseline pre-CAR-T PET/CT): cerebral cortex (8.23 v 7.09, p=0.036), cerebellum (6.26 v 5.56, p=0.024), basal ganglia (9.22 v 7.61, p=0.005), parotid gland (1.61 v 1.42, p=0.004), liver (2.47 v 2.17, p=0.002), spleen (2.08 v 1.84, p=0.043), and pancreas (1.76 v 1.48, p&lt;0.001). No differences in SUVmean were seen in the lung, testes, retroperitoneal or subcutaneous fat, or paraspinal and psoas muscles. A significant increase in cortical activity was seen in patients with CRS grades ≥2 when compared to those with CRS grades 0-1 (Δ2.65 v Δ0.33, p=0.03). No changes in glycolytic activity were observed between patients stratified by CRS in the cerebellum (Δ1.31 v Δ0.36, p=0.12) or liver (Δ0.21 v Δ0.34, p=0.55). In contrast, changes in glycolytic activity were not significantly associated with development of ICANS or with treatment responses. Conclusion: For patients with R/R DLBCL undergoing CD19 CAR-T therapy, significantly increased CNS glycolytic activity is seen on PET/CT at D+30 post-infusion when compared to baseline. Interestingly, these changes do not correlate with development of ICANS or lymphoma response; however, changes in cortical activity were associated with CRS grade ≥2. Overall, our findings illustrate a functional and radiographic link between cytokine release and subsequent disruption of the blood-brain barrier as quantified by increased cortical glycolysis 30 days post-CAR-T therapy. While findings are limited by small sample size, further validation in a larger data set is warranted. Disclosures Hutnick: Kite/Gilead: Other: Yescarta Speakers Bureau, Speakers Bureau. Badros:Celgene Corporation: Consultancy; Amgen: Consultancy.

164 Are Post Oncoplasty Surgical Clips a Reliable Radiographic Surrogate of Tumour Bed Locations? A Phantom Based Study

164 Are Post Oncoplasty Surgical Clips a Reliable Radiographic Surrogate of Tumour Bed Locations? A Phantom Based Study

Prediction of High-Grade Hip Joint Effusion With Simple Radiographs in Children: A Comparative Study With Magnetic Resonance Imaging.

The objective of this study was to investigate the predictive value of asymmetric joint space widening on simple radiographs for the presence of hip joint effusion in children with unilateral hip pain. Sixty-eight patients aged 6 to 17 years with both simple radiograph and magnetic resonance imaging of both hips were retrospectively reviewed. We evaluated the predictive effects of radiographic surrogates for joint space widening on the presence of high-grade hip joint effusion. We also sought to investigate a predictive model for the presence of hip joint effusion with the patients' clinical and radiological data. Radiographic values showed high specificity but low sensitivity for the presence of high-grade joint effusion. On multivariate analysis, sex and the difference ratio of medial and superior gaps were independent predictive factors for unilateral high-grade hip joint effusion. For children 6 years and older with asymmetric hip joint space widening on simple radiographs, further evaluations for the presence of hip joint effusion should be considered because of its high specificity. The predictability can improve if both medial and superior gaps, and sex are included in the evaluation. In girls, hip joint effusion seems to widen the joint space more easily than in boys, which may be owing to the more ligamentous laxity of and less musculature around the hip in girls. However, the risk of joint effusion should not be underestimated even if a child presents symmetry on the simple radiograph because of its low sensitivity and the possibility of bilateral involvements or early stage of diseases.

What is the most accurate and reliable methodological approach for predicting peak height velocity in adolescents? A systematic review

To identify the most accurate method of predicting peak height velocity in adolescents. Systematic review. A comprehensive literature search of six electronic databases and reference lists was conducted. Studies that met selection criteria of (1) observational longitudinal cohort study (2) reproducible method/s of predicting peak height velocity (3) minimum six-month follow-up (4) healthy male and/or female adolescent subjects, with the exception of participants with adolescent idiopathic scoliosis, were considered for review. Studies were screened using a modified quality assessment checklist, with only those scoring >50% included. The type of surrogate measure of peak height velocity, its reliability and ability to predict peak height velocity were extracted from the year or stage immediately preceding peak height velocity. We defined "predict" as when both the estimates of effect and 95% confidence intervals of the surrogate occurred prior to the actual age of PHV. The nine included studies examined three anthropometric, three equation and four radiographic-based surrogates for PHV. Of these, the radiographic measures were reported to exhibit moderate to high intra- and inter-rater reliability. Three of the four radiographic surrogates predicted PHV. Two anthropometric measures also predicted PHV but reliability of the measures is unknown. All equation-based methods predicted the timing of PHV to occur later than it actually happened when applied in the year prior to expected PHV. In the year/stage immediately preceding peak height velocity, radiograph-based methods appear to be accurate and reliable surrogates.

Early Perfusion Computerized Tomography Imaging as a Radiographic Surrogate for Delayed Cerebral Ischemia and Functional Outcome After Subarachnoid Hemorrhage

To date, there is no immediate radiographic surrogate to quantify primary cerebral injury to identify patients at risk for delayed cerebral ischemia and poor clinical outcome after aneurysmal subarachnoid hemorrhage. Therefore, we investigated the relation of early cerebral perfusion-computerized tomography and clot volume with radiological events of delayed cerebral ischemia and clinical outcome in patients with aneurysmal subarachnoid hemorrhage. Data from 2 cohorts of patients (51 in main, 28 patients in control cohort) with aneurysmal subarachnoid hemorrhage, receiving computerized tomography and perfusion-computerized tomography scanning <12 hours after ictus, were included. A risk group model for functional outcome was developed on the basis of early mean transit time (MTT) and volumetric blood clot measurements. The relation of the risk group model with subsequent MTT, angiographic vasospasm, new cerebral infarction, and functional outcome was analyzed. Actual and predicted functional outcomes based on the risk group model were compared in the control cohort. The risk group model correlated significantly with subsequent MTT measurements, cerebral infarction, and functional outcome. Odds for poor outcome were significantly higher in case of concomitant increase of early MTT and clot volumes, as opposed to exclusive early MTT or clot volume increase. For patients in the high- or low-risk groups, neurological outcome in the control cohort correlated significantly with predicted outcomes. Assessment of early cerebral perfusion and intracranial blood clot may serve as a radiographic surrogate for delayed cerebral ischemia and functional outcome in patients with aneurysmal subarachnoid hemorrhage using risk group modeling.

Pulmonary venous occlusion and death in pulmonary arterial hypertension: survival analyses using radiographic surrogates

BackgroundRecent studies find that a considerable number of patients with pulmonary arterial hypertension (PAH) develop fibrous obstruction of the pulmonary veins. Such obstruction more commonly accompanies connective tissue disorder (CTD)-associated PAH than idiopathic PAH. However, few researchers have gauged the risk of death involving obstruction of the pulmonary veins.MethodsThirty-seven patients with PAH were enrolled (18 patients, idiopathic PAH; 19 patients, CTD-associated PAH). The patients were 49 ± 18 years and had a World Health Organization functional class of 3.2 ± 0.6. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were surrogates for obstruction of the pulmonary veins, and were detected by a 16-row multidetector computed tomography scanner.ResultsThe follow-up period was 714 ± 552 days. Fifteen deaths occurred. Thickening of the interlobular septa, centrilobular ground-glass attenuation, and mediastinal adenopathy were found in 37.8%, 24.3%, and 16.2% of patients, respectively. Cox proportional hazard analysis revealed an increased risk of death with each radiographic surrogate (mediastinal adenopathy: p < 0.0001, hazard ratio = 13.9; thickening of interlobular septa: p < 0.001, hazard ratio = 12.0; ground-glass attenuation: p = 0.02, hazard ratio = 3.7). The statistical significance of these relationships was independent of the cause of PAH and plasma concentration of brain natriuretic peptide.ConclusionsThe results of this study imply that obstruction of the pulmonary veins is associated with an increased risk of death in patients with PAH.

The validity of surgical clips as a radiographic surrogate for the lumpectomy cavity in image-guided accelerated partial breast irradiation

Purpose We hypothesize that surgical clips placed in the biopsy cavity during lumpectomy can be used as radiographic markers to facilitate image-guided external beam accelerated partial breast irradiation. Methods and materials We evaluated 28 patients with surgically placed clips in the lumpectomy cavity and two CT scans on different days. To establish whether the clips remain predictive of the lumpectomy cavity throughout therapy, we analyzed the motion of both cavities with repeat volumetric CT scans. The three-dimensional (3D) locations of each lumpectomy cavity and the associated clips were defined as individual regions of interest (ROIs). A single point of interest (POI) was defined for each ROI. The calculated movements of the lumpectomy cavity POIs between different scans were compared to those of the clip POIs. The second CT data set was then moved in accordance to the calculated clip POI's movement. The volume of the (second) lumpectomy cavity associated with the second scan outside of the (first) cavity of the first scan was measured. In addition, the required amount of a radial margin expansion around the first lumpectomy cavity to ensure coverage of the second lumpectomy cavity both before and after moving the second lumpectomy according to the clip POI movement was calculated. Results The two CT scans were obtained on average 27 days apart, and the mean lumpectomy size decreased from 35 to 16 cc. The clip and lumpectomy cavity POIs moved a mean of 3 mm along the three principal Cartesian axes. In moving the second lumpectomy cavity according to the clip POI displacement from its original position, the volume of the second lumpectomy cavity outside of the volume of the first decreased from 2.6 cc to 1.0 cc after correction, and the required radial margin on the first lumpectomy cavity to include the second lumpectomy cavity decreased from 5.5 mm vs. 3.8 mm. Conclusion The surgically placed clips after lumpectomy are strong radiographic surrogates for the biopsy cavity. If the clips were used to guide accelerated partial breast irradiation, a planning target volume margin of the order of 5 mm could be used, significantly smaller than the 10-mm margin currently employed.

The validity of clips as a radiographic surrogate for the biopsy cavity in image-guided accelerated partial breast irradiation

The validity of clips as a radiographic surrogate for the biopsy cavity in image-guided accelerated partial breast irradiation

Apolipoprotein E modulates the CNS response to injury

Apolipoprotein E (apoE) plays an important role in recovery from acute brain injury. One potential mechanism for this is that apoE down‐regulates glial activation and subsequent secretion of inflammatory mediators. Following a pneumatic impact to the closed skull of anesthetized apoE deficient and wildtype mice, MRI was performed to quantify the effacement of the lateral ventricles as a radiographic surrogate for cerebral edema. At 24 hours following injury, apoE deficient animals had a greater degree of cerebral edema as compared to matched controls. This increase in edema was associated with enhanced up‐regulation of TNFα, a pro‐inflammatory cytokine believed to play an important role in mediating blood–brain barrier breakdown and the development of cerebral edema. We have previously demonstrated that a peptide derived from the receptor binding region of apoE retained the anti‐inflammatory activities of the holoprotein in vitro, and we next investigated whether a single intravenous administration of this apoE‐mimetic peptide could exert neuroprotective effects. Thirty minutes after closed head injury, mice were randomized to receive low dose peptide (203 mg/kg); high dose peptide (406 mg/kg), or vehicle. At 24 h post injury, the saline injected animals had a profound deficit in rotorod testing which was associated with weight loss. A single intravenous injection of apoE‐mimetic peptide 30 min following closed head injury protected against motor deficit, weight loss, and neurocognitive deficit in a dose dependent fashion. This suggests that apoE may modify prognosis in brain injury by down‐regulating the CNS inflammatory response, and that mimicking the biological activity of apoE may lead to novel therapeutic strategies in the setting.

Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema.

Apolipoprotein E has been implicated in modifying neurological outcome after traumatic brain injury, although the mechanisms by which this occurs remain poorly defined. To investigate the role of endogenous apolipoprotein E following acute brain injury, noninvasive magnetic resonance imaging was performed on anesthetized mice following closed head injury. Effacement of the lateral ventricle was used as a radiographic surrogate for cerebral edema. At 24 hours following injury, apolipoprotein E-deficient animals had a greater degree of cerebral edema as compared to matched controls. In addition, the brains of apolipoprotein E-deficient animals had a significantly greater upregulation of tissue necrosis factor alpha messenger ribonucleic acid as compared to controls as early as 1-hr post injury. Thus, modulation of the endogenous central nervous system inflammatory response may be one mechanism by which apolipoprotein E affects outcome following acute brain injury.