2nd Scan Research Articles

#2974 Serial multiparametric magnetic resonance imaging in a prospective cohort of patients with acute kidney injury

Abstract Background and Aims Recovery from acute kidney injury (AKI) is traditionally measured using serum creatinine but this can often over-estimate the degree of renal recovery. It is known, however, that failure of recovery of serum creatinine 90 days after AKI strongly associates with subsequent long-term reductions in renal function making it an important clinical timepoint. Magnetic resonance imaging (MRI) is an imaging modality with promise to improve the understanding and characterisation of renal pathophysiology. In a single multiparametric MRI (mpMRI) scan, multiple measures can assess renal morphology, tissue microstructure (T1 relaxation time and diffusion-weighted-imaging (DWI)), oxygenation, perfusion and blood flow. We previously published the first study of renal mpMRI at the time of AKI and during follow up, this showed increased total kidney volume (TKV) and T1 as a measure of inflammation/fibrosis at the time of AKI which remained elevated in some participants at 3 and 12 months despite normalisation of serum creatinine. This study aimed to assess the degree of change between 30 and 90 days post AKI, as the first 90 days after AKI appear to be the important in terms of outcomes. Method Prospective observational study of 10 participants with AKI of all stages recruited at the time of AKI and followed up with monthly bloods and urine. MRI scans were collected on a Philips Ingenia 3T at day 30-60 and day 90. The 1-hour protocol included: T2-weighted scans for automated segmentation to compute total kidney volume (TKV), as well as T1 & T2 mapping, DWI, ASL and phase contrast MRI for kidney perfusion and blood flow, and TRUST-MRI and BOLD R2* for kidney oxygenation, and MRE for stiffness. Results 10 participants were scanned at 2 timepoints, (mean day 45 for 1st scan, 95 for 2nd scan). Baseline characteristics are summarised in Table 1 along with key clinical measures in Table 2. 2 participants had CKD at baseline. Despite a range of peak creatinine values and AKI stages the majority of participants serum creatinine normalised to within 20% of baseline by 30 days (v3) (Fig. 1). Fig. 2 shows the TKV for AKI patients across the 2 visits as compared with healthy values. Despite normalisation of biochemistry, 5 participants had enlarged TKV. The predominant AKI aetiology for these patients was sepsis. Across all participants there is little dynamic change between visits. The participant with the small TKV across both visits had pre-existing CKD, as well as the highest peak creatine. The participant did not recover renal function by day 90 (Figs 1(j) and 2). Conclusion Despite recovery of biochemistry, at least half of this AKI cohort had abnormal MR measures at that persisted through one and three months after the AKI episode. There is a trend towards larger TKV in patients with AKI due to sepsis, which needs to be explored in a larger cohort. Analysis of more parameters as well as the addition of liquid biomarkers will enrich these preliminary findings.

Multi-phase contrast-enhanced magnetic resonance image-based radiomics-combined machine learning reveals microscopic ultra-early hepatocellular carcinoma lesions

PurposeThis study aimed to investigate whether models built from radiomics features based on multiphase contrast-enhanced MRI can identify microscopic pre-hepatocellular carcinoma lesions.MethodsWe retrospectively studied 54 small hepatocellular carcinoma (SHCC, diameter < 2 cm) patients and 70 patients with hepatocellular cysts or haemangiomas from September 2018 to June 2021. For the former, two MRI scans were collected within 12 months of each other; the 2nd scan was used to confirm the diagnosis. The volumes of interest (VOIs), including SHCCs and normal liver tissues, were delineated on the 2nd scans, mapped to the 1st scans via image registration, and enrolled into the SHCC and internal-control cohorts, respectively, while those of normal liver tissues from patients with hepatocellular cysts or haemangioma were enrolled in the external-control cohort. We extracted 1132 radiomics features from each VOI and analysed their discriminability between the SHCC and internal-control cohorts for intra-group classification and the SHCC and external-control cohorts for inter-group classification. Five radial basis-function, kernel-based support vector machine (SVM) models (four corresponding single-phase models and one integrated from the four-phase MR images) were established.ResultsAmong the 124 subjects, the multiphase models yielded better performance on the testing set for intra-group and inter-group classification, with areas under the receiver operating characteristic curves of 0.93 (95% CI, 0.85–1.00) and 0.97 (95% CI, 0.92–1.00), accuracies of 86.67% and 94.12%, sensitivities of 87.50% and 94.12%, and specificities of 85.71% and 94.12%, respectively.ConclusionThe combined multiphase MRI-based radiomics feature model revealed microscopic pre-hepatocellular carcinoma lesions.

Relationships between the Fear of COVID-19 Scale and regional brain atrophy in mild cognitive impairment.

Several studies have reported that the pandemic of coronavirus disease 2019 (COVID-19) influenced cognitive function in the elderly. However, the effect of COVID-19-related fear on brain atrophy has not been evaluated. In this study, we evaluated the relation between brain atrophy and the effect of COVID-19-related fear by analysing changes in brain volume over time using magnetic resonance imaging (MRI). Participants were 25 Japanese patients with mild cognitive impairment (MCI) or subjective cognitive decline (SCD), who underwent 1.5-tesla MRI scan twice, once before and once after the pandemic outbreak of COVID-19, and the Fear of Coronavirus Disease 2019 Scale (FCV-19S) assessment during that period. We computed regional brain atrophy per day between the 1st and 2nd scan, and evaluated the relation between the FCV-19S scores and regional shrinkage. There was significant positive correlation between the total FCV-19S score and volume reduction per day in the right posterior cingulate cortex. Regarding the subscales of FCV-19S, we found significant positive correlation between factor 2 of the FCV-19S and shrinkage of the right posterior cingulate cortex. There was positive correlation between the FCV-19S score and regional brain atrophy per day. Although it is already known that the psychological effects surrounding the COVID-19 pandemic cause cognitive function decline, our results further suggest that anxiety and fear related to COVID-19 cause regional brain atrophy.

A deep CNN‐based approach for predicting MCI to AD conversion

AbstractBackgroundDeep convolutional neural networks (CNNs) have demonstrated a considerable ability to decode various biomedical signals, including 2D and 3D neuroimaging data. Magnetoencephalography‐based functional connectivity (MEG‐FC) is proven to be a useful tool in predicting the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD), since early signs of AD may be hidden in the way neuronal activity is spatially distributed and coordinated among different brain regions. In the present work, we propose a deep learning approach for the early diagnosis of AD, able to capture the electrophysiological anomalies occurring before the conversion by exploit an image‐based coding of MEG‐FC data. The proposed approach has been tested on a set of resting‐state MEG recordings, from a longitudinal study (24 months between 2 MEG scans for each subject) involving 54 participants: 27 'progressive' patients (i.e., MCI at the time of the 1st scan converted to AD at the time of the 2nd scan), and 27 'static' patients (i.e., MCI at the time of the 1st scan remained MCI at the time of the 2nd scan).MethodMEG and MRI data have been gathered from the 54 patients using an Elekta Vectorview system and a General Electric 1.5T MRI scanner, respectively. Source reconstruction was performed with LCMV beamformer. The obtained neural MEG sources were anatomically parcellated into 90 ROIs according to the AAL atlas. Considering the signals stemming from the 90 ROIs we extracted the MEG‐FC measures (PLV and COR), for different frequency bands [Hz]: θ(4‐8), α(8‐12), β(12‐30), and γ(30‐55). MEG‐FC has been then coded into image‐based representations and hierarchically decomposed by means of the CNN layers of 'AlexNet'. Finally, different classification techniques have been tested as predictive modules.ResultWith the proposed approach we obtained an accuracy of 0.9 in discriminating ‘static’ from ‘progressive’ patients using MEG‐FC data from the first scan. The best classification results have been obtained using the Linear Discriminant Analysis and Support Vector Machine techniques.ConclusionThe classification of FC profiles mediated by hierarchical CNNs decomposition is a promising method for detecting the early neurophysiological anomalies characterizing the progression to AD.

Alternative measure of therapy impact (TXI): Length of sojourn on treatment—Value of early restaging imaging for prediction of response to nivolumab among patients with advanced cancer.

106 Background: Cross-sectional Imaging (CI) plays an essential role in early assessment of patients on immune checkpoint inhibitors (ICIs), yet often remains inconclusive in the setting of advanced disease, prior cancer treatment, toxicity, and cancer unrelated findings. We propose a robust, reproducible imjScore based on measurable tumor response on the first two re-staging scans that may predict TXI. We are testing prognostic value of early imaging, time lag of ICIs effect, against Duration of clinically effective treatment as a Measure of Treatment Impact. Methods: Retrospective review of CI studies in 92 patients with advanced stage solid tumors treated with Nivolumab (Nivo) during 6/2015-8/2018 at BMC on standard clinical protocols. Time on therapy (TOTx) was used as a surrogate marker of therapy impact. Modified imRECIST score utilizing ∑ of 5 discrete cancer lesions at baseline, 1st, and 2nd CI since initiation of Nivolumab were adjusted for TOTx. Our imjSCORE averages "predicted days on therapy" from best fit function of tumor change/day [%] at each time point vs. TOTx and ratios between 1st and 2nd scan. Results: Median TOTx was 70 days (range 1-1029). Differences in imRECIST scores derived from two early restaging CI studies adjusted for TOTx were able to identify with high statistical significance two groups of "SHORT" vs "LONG" sojourn on Nivolumab around Median of 70 days. Early Progression curve was associated with shorter benefit of Nivo; Pseudo-progression curve showed significantly shorter sojourn on Nivolumab compared to initial Regression or Stable score curves (P &lt; .002). Conclusions: The imjScore may differentiate with high likelihood patients with short versus long sojourn on Nivo as a novel measure of TXI. Our CI-based imjSCORE validates early imaging with a response curve and standardized analysis of the 1st and 2nd post-treatment scans. If validated with other ICIs, this scoring tool may allow early prediction of ICIs treatment response and clinical outcome. Further correlation with clinical biomarkers may lead to development of predictive nomograms of "short" versus "long" TXI.

Development of imjSCORE for early prediction of response to nivolumab among patients with advanced cancer.

e14169 Background: Cross-sectional Imaging (CI) plays an essential role in early assessment of patients on immune checkpoint inhibitors (ICIs), yet often remains inconclusive in the setting of advanced disease, prior cancer treatment, toxicity, and cancer unrelated findings. Best timing of scans is also uncertain and may affect interpretation. We propose here a robust, reproducible imjScore based on measurable tumor response on the first two re-staging scans and their ratios that may predict treatment impact. Our approach incorporates the prognostic aspect of early imaging, time lag of ICIs effect, and alternative measures of treatment impact. Methods: Retrospective review of CI studies was performed in 92 patients with advanced stage solid tumors treated with Nivolumab during 6/2015-8/2018 at Boston Medical Center utilizing standard clinical protocols. Time on therapy (TOTx) was used as a surrogate marker of therapy impact. Modified imRECIST score utilizing Σ of 4 discrete cancer lesions at baseline (&lt; 1 month before Nivolumab), 1st, and 2nd CI since initiation of Nivolumab were adjusted for TOTx. Our imjSCORE averages "predicted days on therapy" calculated from best fit function of tumor change/day [%] at each time point vs. TOTx and ratios between 1st and 2nd scan. Results: Median TOTx was 70 days (range from 1 to 1029). Differences in imRECIST scores derived from two early restaging CI studies adjusted for TOTx were able to identify with high statistical significance two groups of "SHORT" vs "LONG" sojourn on Nivolumab based on Median of 70 days. Early progression curve was associated with shorter benefit of Nivolumab; subset with pseudo-progression curve showed still significantly shorter sojourn on Nivolumab compared to initial regression or stable score curves (P &lt; .002). Conclusions: The development of imjScore may differentiate with high likelihood patients with short versus long sojourn on Nivolumab. Our CI-based evaluation using the imjSCORE suggests a clear benefit from early imaging with a response curve and standardized point analysis of the 1st and 2nd post-treatment scans. If validated with other ICIs, this scoring tool may allow early prediction of ICIs treatment response and clinical outcome. Further correlation of imjSCORE with clinical biomarkers may be useful to build predictive nomograms of "short" versus "long" treatment impact.

Longitudinal changes of amygdala functional connectivity in adolescents prenatally exposed to cocaine

BackgroundPrenatal cocaine exposure (PCE) is associated with arousal dysregulation, but interactions between exposure and age are rarely investigated directly with longitudinal study designs. Our previous study had examined task-elicited emotional arousal and noted persistently high amygdala activations in the development of adolescents with PCE. However, while externally imposed emotional arousal could be considered a “state” effect depending on specific task stimuli, it is still unclear whether similar developmental alterations extend to intrinsic functional connectivity (FC), reflecting more of a “trait” effect. MethodsWe used a longitudinal design and analyzed resting-state functional magnetic resonance imaging data acquired twice from 25 adolescents with PCE and 16 non-exposed controls. Both groups were each scanned first at the mean age of 14.3 and then again at 16.6 years. Seeding in bilateral amygdalae and comparing the 2nd scan with the 1st, we examined the interaction effect between PCE and age on FCs in the emotional network. ResultsCompared with the younger age, we observed a generally decreased FC in the emotional network of the control group at the older age, but these FCs were generally increased at the older age in this same network of the PCE group. Additionally, this interaction effect of exposure by age in the right fusiform was positively correlated with the emotional interference imposed by external task stimuli. ConclusionsThese results provided additional data directly characterizing developmental changes in the emotional network of adolescents with PCE, complementing and extending the notion of a PCE-associated long-term teratogenic effect on arousal regulation.

P06.08: Prediction of emergency Caesarean sections: which variables are important?

To explore the relationship between intrapartum variables and emergency Caesarean section (EMCS) rates. Term nulliparous women recruited in early labour, an admission scan performed to include transabdominally umbilical and middle cerebral artery, fetal head position and on transperineal scan- head perineum distance, caput and moulding. The scan was repeated with the next vaginal examination (VE), ideally 4 hours apart. This scan included an abdominal scan for fetal head position and transperineal scan for head perineum distance, caput and moulding. Cervical dilatation was documented from the corresponding digital VE. 1st scan predictors of EMCS were maternal age, BMI, gestational age, umbilical-cerebral ratio, moulding, HPD, rotation, cervical dilatation and caput. 2nd scan predictors were HPD decrease/hr, rotation improvement/hr, dilatation increase/hr and caput increase/hr. A univariable analysis was performed; each predictor was related to EMCS in a simple logistic regression analysis. Next, a multivariable analysis was performed to investigate which variables were most predictive. One model was constructed on all patients, using baseline and first scan measurements. Another model was constructed on patients with two scans, including second scan measurements as predictors. April 2015-Jan 2018, 270 patients were recruited of which 1 withdrew consent. Of 269 patients, 50(19%) had only a single scan. EMCS was required in 79/269 patients (29%) overall: 69/219 patients with two scans (32%) and 10/50 patients with a single scan (20%). Cervical dilatation change was the most important variable for predictive ability(p<0.0001) and was deduced from 2 scans, followed by a ‘spot’ cervical dilatation, HPD, and caput(p<0.0001) from one scan. A model with these 4 variables had an apparent AUC=0.82. This is the first study to comprehensively quantify the extent to which repeat maternal and intrapartum variables are related to EMCS deliveries longitudinally. When validated externally, these data will inform the development of a more robust prediction model for EMCS. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

The Status of Stress Myocardial Perfusion Imaging Using 99mTc Pharmaceuticals in Japan: Results from a Nationwide Survey.

Objective(s):To appropriately use one-day myocardial perfusion imaging (MPI) with 99mTc radiopharmaceuticals (i.e. to avoid shine-through artifacts), injection doses need to be optimized and dose ratios between the 1st and 2nd scans should be maintained at ≥ 3. However, the current state of practice in Japan is unclear. Thus, the aim of this study was to clarify the details of MPI protocols using 99mTc radiopharmaceuticals in Japan. Methods: A nationwide survey was conducted in June and July 2016. Questionnaires about stress MPI protocols using 99mTc radiopharmaceuticals were sent to 641 nuclear medicine facilities. Results:Responses were received from 246 facilities. One-day protocols were used in 97.1% of the facilities. The most common injection dose ratio was 2.5. Only 18.2% of facilities achieved the recommended injection dose ratio. Stress-only protocols were performed in only 1.7% of facilities; the primary reasons for not performing stress-only protocols were as follows: 1) “The reading-physician cannot interpret the image just after the first scan,” and 2) “Preparation of radiopharmaceuticals and scan arrangements turn out to be complicated.”Conclusion: Approximately 80% of nuclear medicine facilities do not follow the recommended injection dose ratio. Stress-only protocols are ideal, but are performed at very few facilities. Both optimization and standardization of stress MPI protocols using 99mTc radiopharmaceuticals are needed in Japan.

Formation of the calcarine sulcus: a potential marker to predict the progression in utero of isolated mild fetal ventriculomegaly.

Our previous study confirmed the negative association between the development of calcarine sulcus and the width of lateral ventricles. The purpose of current study was to evaluate the reliability of calcarine sulcus depth in the 2nd trimester to predict the prenatal enlargement of lateral ventricle in fetuses with isolated mild fetal ventriculomegaly (IMVM).This study used a retrospective cohort study design. A total of 97 pregnant women with IMVM diagnosed between 20 and 26 weeks’ gestation returned for a 2nd examination at 30 to 32 weeks. Lateral ventricular size and calcarine sulcus depth were acquired from ultrasonography and magnetic resonance imaging (MRI) scans, respectively. Progression was defined as the process of developing from a lower group toward a higher (<10 mm, 10–12 mm, 13–15 mm, and ≥16 mm).Significant correlation was observed between calcarine sulcus depth and ventricular measurements at the 2nd scan (r = −0.71, P < .0001). Receiver-operating characteristic curves showed that calcarine sulcus depth (area under curve [AUC] = 0.83, 95% confidence interval [CI] = 0.74–0.92) had the best diagnostic performance in predicting the prenatal progression, as compared with lateral ventricle width (AUC = 0.69, 95%CI = 0.54–0.84) and gestational age (AUC = 0.70, 95%CI = 0.57–0.83) at the initial scan. The cutoff value for calcarine sulcus depth was 3.3 mm, with the corresponding sensitivity and specificity were 75.0% and 81.3%, respectively. Multivariate analyses showed that calcarine sulcus depth ≥3.3 mm (odds ratio = 0.09, 95%CI = 0.02–0.38, P = .001) was an independent predictor of the prenatal progression.For IMVM, calcarine sulcus depth might be a powerful marker to identify subjects at higher risk for worse prenatal progression.

Moisture-Mediated Interactions Between Amorphous Maltodextrins and Crystalline Fructose.

The effects of coformulating amorphous maltodextrins (MDs) and crystalline fructose, a deliquescent solid, on the moisture sorption, deliquescence point (RH0 ), and glass transition temperature (Tg ) behaviors were determined. Moisture sorption profiles of binary fructose:MD mixtures and individual ingredients were generated using controlled relative humidity (RH) desiccators and by dynamic vapor sorption techniques. Blends exhibited synergistic moisture uptake at RHs below the RH0 of fructose, attributed to partial dissolution of fructose in plasticized MD matrices without a significant reduction in the RH0 of the undissolved fructose. Increasing storage temperature decreased the onset RH for moisture sorption synergy. At all storage RHs, the measured Tg (2nd scan) was significantly reduced in fructose:MD mixtures compared to individual MDs, and was related to both the synergistic moisture uptake in the blends and heat-induced ternary fructose-MD-water interactions in the differential scanning calorimeter. Differences were found between the behavior of fructose:MD blends and previous reports of sucrose:MD and NaCl:MD blends, caused in part by the lower RH0 of fructose. The enhanced moisture sorption in blends of deliquescent and amorphous ingredients could lead to problematic moisture-induced changes if storage conditions are not controlled.

Measure bone volume and density changes of sites grafted with bone allografts and a titanium mesh on cone-beam computed tomography: a technique.

The aim of this study was to introduce a novel method to evaluate volumetric and density changes of the augmented sites. A ridge augmentation procedure, using particulate bone allografts and a titanium mesh, was performed on the posterior edentulous mandible of 3 participants. Cone-beam computed tomography was taken preoperatively (1st scan), immediately (2nd scan), and 5 months (3rd scan) after the surgery. The grafted area was segmented on the 2nd and 3rd scans, using the 1st scan as the reference. The volume of the grafted area and the newly formed bone-graft complex that is defined by a preselected threshold was then determined. The bone mineral density (BMD) of the grafted area was determined by comparing gray-scale histograms of the grafted area for the 2nd and 3rd scans using the cortical bone adjacent to the grafted area as the reference. The mean volumetric shrinkage was 13.5%. The BMD increase was 4.65%. The mean error in determining cortical bone density between the scans was 1.69%. A novel technique to measure bone volume and density changes after bone augmentation was described. The low measurement/scanning error suggested that this technique is reliable and reproducible.

WE-G-134-02: BEST IN PHYSICS (IMAGING) - Extend the CBCT Volumetric Coverage Using a Pair of Circular Scans with Complementary and Opposite Detector Lateral and Longitudinal Shifts

Purpose: Volumetric coverage of current CBCT system is limited by machine mechanical configurations and detector panel size. To address this problem, we developed a novel CBCT image acquisition method, DSCS (Dual Scan with Complementary Shifts) by using a pair of complementary circular CBCT scans with lateral shifts and opposite longitudinal shifts of the detector panel, combined with complementary longitudinal shifts of the couch table, to provide up to 40 cm longitudinal coverage and a 45 cm field‐of‐view (FOV). Methods: The two source positions are up to 40 cm apart in the longitudinal direction. In the 1st scan, the detector panel is shifted inferiorly and its superior edge is aligned with the 1st source position. In the 2nd scan, the panel is shifted superiorly and its inferior edge is aligned with the 2nd source position. The detector is shifted laterally by 16 cm to obtain a 45 cm FOV. Opposite lateral detector displacements are used to improve image quality by providing complementary information. To support DSCS, we have developed a new filtered‐back‐projection (FBP) CBCT image reconstruction algorithm to create images from the overlapped and shifted projection data of the dual scans together. Results: We have successfully implemented the proposed DSCS CBCT acquisition method on a Varian TrueBeam radiation therapy treatment machine in the research mode. Satisfactory results were obtained for a human body phantom. Conclusion: The complementary pair scans provide a promising solution to the longitudinal coverage and effective use of imaging dose. The efficiency of imaging dose usage is near 100% and there is no imaging dose outside the effective longitudinal coverage. This new CBCT method could be useful to facilitate clinical applications including image guidance and treatment adaptation. Supported by a research agreement with Varian Medical Systems.

Abstract TP42: Brain Plasticity Changes in Default Mode Network after Stroke

Background: Resting-state fMRI (rs-fMRI) has been used for assessing task-free brain activity changes after stroke. One prominent resting-state neural network is the default mode network (DMN) that has been suggested to be suppressed during cognitive tasks. Older adults often show difficulties in suppressing DMN compared to younger adults during cognitive task performance. Moreover, dysfunction of DMN appears to be linked with the severity of post-stroke depression. Here we explored brain plasticity changes in DMN in stroke subjects. Methods: 9 stroke subjects (mean age=60.3, 5 Male) and 5 normal healthy subjects (mean age=48, 4 Male) underwent two rs-fMRI scans. Patients participated in the 1st scan within 7 days after onset and within 6 months (mean ~3 months) postonset in the 2nd scan. Brain plasticity changes were examined by functional connectivity measures that were computed using region-of-interest analysis. Rs-fMRI data were pre-processed in AFNI. The resulting time-series from 6 common seeds in DMN were averaged over each seed and correlated with that from every other seed to generate the Pearson correlation coefficients. These correlations were then z-transformed representing the 15 unique functional connections (fconn) in DMN. Fconn changes were determined with intraclass correlation (ICC), which measures reproducibility of fconn between scans. A reliable connection, as suggested to be an ICC ≥ 0.5, requires a small within-subject plasticity change compared to the between-subject variance. Results: Shown in Table 1. Conclusion: As seen from Table 1, fconn between RtLatPar and PC may undergo plasticity changes after stroke (ICC &lt; 0.5) as would be reliable in the normal group. Fconn between LtLatPar and PC, mPFC and PC, right and left LatPar were found to be significant and reliable, which could be due to less suppression in DMN and higher between-subject variability after stroke.

Modern imaging technique assessment of small cell lung cancer doubling time.

e17561 Background: Doubling time in non-SCLC tumors has been well studied, but this is less so in SCLC. We aim to study in vivo doubling time in SCLC using modern imaging techniques. Methods: Patients (pts) with SCLC with both diagnostic computed tomography (CT) and subsequent staging Positron Emission Tomography (PET)/CT were identified from institutional database. Primary lesion and nodal disease on the initial CT scan and on the CT component of PET/CT scan was measured. Diameter Doubling Time (D-DT) = [(dt)*log 2] / [3(log D2 – log D1)], where dt was time interval between scans, D2 and D1 are diameters of lesion on second and first scan respectively. Volume Doubling Time (V-DT) = [(dt)*log 2] / (log V2 – log V1), where V2 and V1 are volume of 2nd and 1st CT. Results: 18 eligible pts were identified. 61% were males, median age 63. Primary lesion was assessable in 14 pts and nodal disease in 17. Mean interval between scans was 19.7 days (range: 6 – 67). Mean diameter of primary lesion on 1st and 2nd scans: 4.17 cm +/- 2.11 and 4.63 cm +/- 2.26. Mean diameter of lymph nodes on 1st and 2nd scans: 4.24 cm +/- 1.72 and 4.78 cm +/- 1.81. Mean volume of primary lesion on 1st and 2nd scans: 35.56 cm3 (=/- 43.34) and 45.52 cm3 (+/- 55.66). Mean volume of nodal disease on 1st and 2nd scans: 32.77 cm3 (+/- 44.52) and 44.16 cm3 (+/- 55.06). For primary tumor, mean D-DT was 70.0 days +/- 16.4, with mean V-DT 60.5 days +/- 11.8, p=.64. There is a significant correlation between D-DT and V-DT with Pearson rho of 0.7691 (p=0.0013). For nodal disease, mean D-DT = 51.1 days +/- 15.1 and mean V-DT 42.2 days +/- 9.3, p= .62, with correlation between D-DT and V-DT, Pearson rho of 0.7609, p=.0004. There was higher doubling time in extensive stage (ES) SCLC primary tumors compared with limited stage (LS), with mean D-DT 24.0 days vs 97.6 days, p=.046. When all lesions analyzed collectively, mean D-DT = 59.6 days, 95% CI 37.1 – 82.2 and mean V-DT = 50.5 days, 95% CI 35.3 – 65.7. Conclusions: Our data demonstrate more rapid doubling time of SCLC compared to historical data. The differential in growth between LS and ES points to a biologic dichotomy. This has a significant impact in the timely management of SCLC, and potential avenues for therapeutic development.

123 Cardiovascular risk in asymptomatic potential simultaneous pancreas-kidney transplant recipients is determined by myocardial perfusion scintigraphy

Introduction More than 50% of renal transplant recipients will die as a consequence of cardiovascular disease (CVD). Type I diabetics undergoing simultaneous pancreas-kidney transplantation (SPK) are at an even greater risk of CVD. Optimising a patient′s cardiovascular status is necessary before SPK transplant surgery. Patients can remain on transplant waiting lists for years. There is little evidence as to how frequently repeat cardiovascular risk assessments are required in asymptomatic patients. Myocardial perfusion scintigraphy is used in SPK patients to detect any asymptomatic myocardial ischaemia or abnormal left ventricular function. This study analyses data from a SPK transplant centre with an annual surveillance programme to aim to establish the suitable frequency of MPS. Methods Potential SPK transplant recipients who had undergone two perfusion scans were included for analysis. An abnormal MPS was defined as either showing a regional wall motion abnormality, inducible ischaemia, or impaired left ventricular function. The scan results were both documented and compared. Angiography results from the study period were also recorded. Results 99 out of 130 patients on the SPK waiting list in November 2009 had undergone two perfusion scans as part of their pre-transplant assessment. The median age was 45 yrs (range 26–63), with 41% female and a median time between scans of 1.4 yrs (range 0.6–3.0). 59 patients (60%) had two consecutive normal scans. The remaining 40 patients had at least one abnormal scan. 16% of patients with a normal 1st scan developed an abnormal 2nd scan within a median period of 1.4 years. 28 (70%) of the patients with an abnormal MPS underwent angiography, of these 12 required revascularisation (either PCI or CABG). Of the remaining 16 patients; 1 died before angiography and the other 15 patients were treated with medical therapy. Of the 59 patients with two normal scans; 3 underwent angiography during the study period (for new symptoms), 1 of these patients required revascularisation after presenting with an ACS. 2 had minor plaque disease. Conclusions 40% of SPK patients on the waiting list have an abnormal MPS. Of the patients with normal scans 5% required an angiogram because of new symptoms with only 2% requiring revascularisation. Of the patients undergoing angiography driven by MPS 43% subsequently underwent revascularisation. The current screening interval is successfully monitoring changes in the patients9 cardiovascular status with only one patient requiring an intervention which was not predicted by MPS. Therefore a near annual MPS is a useful, non-invasive means by which to monitor patients at very high risk of asymptomatic cardiovascular disease while awaiting a SPK transplant.

Assessing joint vibration during spinal manipulation

This IRB‐approved study assessed the relationship between cavitation and zygapophysial (Z) joint gapping following spinal manipulation (adjusting) in 5 healthy volunteers. High signal MRI markers were used to accurately identify the T12, L3, and S1 spinous processes during scout views. Axial images of the L4/L5 and L5/S1 levels were obtained in the neutral supine position. Each subject was then positioned on the side, and accelerometers were placed over the marked spinous processes. Recording from the accelerometers was done from final positioning through adjusting. The subject was then scanned in side posture position (accelerometers removed). Using a digitizer, the greatest A‐P central Z joint articular surface distances were measured on the 1st and 2nd scans; the difference between the 2 measurement values was the gapping difference, GD; a positive value indicating an increase in gapping following the spinal adjustment. GD was compared between up‐side (adjusted), down‐side (non‐adjusted), cavitation, and non‐cavitation joints.ResultsGD was increased in Z joints that were adjusted [0.5 (SE 0.2) mm] vs. non‐adjusted [−0.2 (SE 0.2) mm], and vertebral segments with cavitation gapped more than no cavitation [0.8 (SE 0.4) vs. 0.4 (SE 0.2) mm].ConclusionsA future clinical study is quite feasible. Forty subjects would be needed for appropriate power (0.80). Funding: NIH/NCCAM (#2R01AT000123).

SU‐FF‐I‐157: Activity Quantification of Micro PET Imaging Using Hollow Spheres in a Small ECT Phantom

Purpose: To evaluate quantification of F‐18 activity distribution in Micro PET images of a set of hollow spheres inserted in a small ECT phantom. Method: Six hollow spheres (Data Spectrum Micro Spheres: diameter: 12.43, 9.89, 7.86, 6.23, 4.95 and 3.95 mm) in a cylindrical phantom (net volume: 110 mL with cold rods insert) were injected with F‐18 and imaged using a Micro PET scanner (Rodent R4. Concorde Microsystems). Hollow sphere activities were prepared in one syringe for the same activity concentration and measured with a dose calibrator as 153, 102, 52, 22, 19 and 7 uCi respectively. Two sets of images were acquired using the same protocol. Second imaging started 65 minutes after completion of the first scan to compare dead time effect. Each 20‐minute scan was set to reduce statistical fluctuation. Image reconstruction used a 3‐D reprojection method with Fourier rebinning. Region of interests of the hollow spheres were defined manually on the 1st scan and then copied to the 2nd image for consistency. Result: True count rate dropped from 445 kcps, 44% dead time (1st scan) to 280 kcps, 27% dead time (2nd scan). About 5.5% decrease was due to dead time. Significant partial volume effect appeared for spheres with diameter less than 6 mm. Recovery coefficient curve was generated for quantification of brain image of rats. Total activities in the spheres were consistent with both images, and agreed with readings from the dose calibrator. Conclusion: Phantom imaging could be used to generate recovery curve and calibration factors that are necessary for quantification of small animal scans. Partial volume effect starts when the object size is much greater than the camera spatial resolution that is measured with point or line source in air.

Bone density changes during adjuvant aromatase inhibitor treatment in breast cancer patients: Single center experience

e11565 Background: Adjuvant aromatase inhibitors (AI) therapy in breast cancer accelerates bone loss resulting in increased incidence of fracture. We evaluated the effect of AI on bone density changes among breast cancer patients. Method: A total of 85 patients who had adjuvant AI for more than 24 months and 3 Dual energy X-ray Absorptiometry (DXA) scans were included in this study. Annual bone density change was calculated and correlated with various risk and prognostic factors. Results: Adjuvant AI was given in up-front (50), sequential (15) and extended adjuvant (17) therapy settings, with a median duration of 31 months. Intervals between scans varied from 6 - 33 months (median = 13 months), 63 patients had baseline DXA scans undertaken within 6 months from start of AI. Bisphosphonate was prescribed to 35 patients during AI therapy according to local practice. Changes in bone density according to WHO classification is shown in the table. Annual bone density change in the spine at 2nd scan was (-9.2% to +11%, mean = -0.89±4.11), after 3rd scan, (-11.7% to +10.7%, mean = 0.021±3.84). In the group of patients who had adjuvant chemotherapy (59 patients), significant bone loss was seen in the patients who did not have bisphosphonate (n=39), (-0.011 in BMD, Mean=0.88±0.02) compared to those who had bisphosphonate (n=20), (0.036 in BMD, Mean=0.93±0.02). In the patients who did not have chemotherapy (n=26), no bone loss was seen whether bisphosphonate was used or not. No clinical bone fracture was reported among patients who had osteoporosis at baseline. Conclusions: The patients who had chemotherapy are more likely to lose bone density and close monitoring is required for bisphosphonate therapy. Bone loss is more significant in the lumbar spine compared to the hip. Following intervention with bisphosphonate, the rate of bone loss was reduced, and as a result only 2.3% of patients developed osteoporosis during AI treatment. AI can be safely given from the bone health point of view with the appropriate use of bisphosphonate. [Table: see text] No significant financial relationships to disclose.

Bisphosphonate therapy requirement during adjuvant aromatase inhibitor therapy in early breast cancer patients according to UK bone health guidelines

e11612 Background: Adjuvant aromatase inhibitor (AI) therapy increases bone loss and incidence of bone fracture. Recently published UK bone health guidelines recommend to prescribe bisphosphonate (BPN) during adjuvant AI therapy for T score of -2 or less, or annual loss of bone density &gt;4%, or known vertebral fracture, or patients over the age of 75 with one or more clinical risk factors (previous low-trauma fracture after age 50, previous hip fracture, alcohol intake of &gt;4 units/ day, diseases associated with secondary osteoporosis, prior corticosteroids for &gt;6 months, BMI &lt;22). We evaluated the impact of BPN therapy requirement using UK guidelines on adjuvant AI therapy patients. Methods: Patients who were commencing adjuvant AI therapy for early breast cancer underwent Dual energy X-ray Absorptiometry (DXA) bone density assessment, with a baseline scan and 2 subsequent scans. Results: A total of 91 patients were eligible and included in this study (median age 59). Different AIs included anastrozole(68), exemestane (7) and letrozole (16). Patients received AI therapy in up-front (56), sequential (15) and extended adjuvant (20) therapy settings. Median duration of AI therapy was 35 months, with 85 patients having received therapy for more than 24 months. BPN was prescribed to 35 patients during AI therapy as per local practice. According to WHO classification, 11 patients were found to have osteoporosis at the 1st scan, and 4 &amp; 2 patients were found to develop osteoporosis at 2nd &amp; 3rd scans, respectively. According to UK guidelines, however, BPN therapy would be indicated in 56 patients (62%): after 1st scan 22 patients, after 2nd scan another 26 patients and following the 3rd scan an additional 8 patients. Factors predictive of BPN indication during AI therapy are hyperthyroidism (p = 0.009), previous fracture (p = 0.001) and smoking (p = &lt;0.001). Patients who took tamoxifen for more than one year are less likely to require BPN compared to those who did not take tamoxifen (p = 0.028) Conclusions: Majority of patients (up to 62% in our study) will require BPN during adjuvant AI for breast cancer. Therefore the cost of BPN and potential drug side effects need to be taken into account in the use of adjuvant AI, and it's health economic analysis. No significant financial relationships to disclose.