177Lu-PSMA SPECT Quantitation at 6 Weeks (Dose 2) Predicts Short Progression-Free Survival for Patients Undergoing 177Lu-PSMA-I&T Therapy.

177Lu-PSMA is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC). Our ability to assess response rates and adjust treatment may be improved using predictive tools. This study aimed to evaluate change in 177Lu-PSMA SPECT quantitative parameters to monitor treatment response. Methods: One hundred twenty-seven men with progressive mCRPC previously treated with androgen-signaling inhibition (99%) and chemotherapy (71%) received a median of 3 (interquartile range [IQR], 2-5) 8-GBq (IQR, 8-8.5 GBq) doses of 177Lu-PSMA-I&T. Imaging included 68Ga-PSMA-11 PET/CT (SUVmax > 15 at a single site and > 10 at all sites > 2 cm), diagnostic CT, and 177Lu SPECT/CT from vertex to mid thigh (24 h after treatment). 177Lu SPECT/CT quantitative analysis was undertaken at cycles 1 (baseline) and 2 (week 6) of treatment. Clinical and biochemical results were assessed to evaluate prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival (OS). Results: A PSA reduction of more than 50% was seen in 58% (74/127). The median PSA PFS was 6.1 mo (95% CI, 5.5-6.7), and OS was 16.8 mo (95% CI, 13.5-20.1). At the time of analysis, 41% (52/127) were deceased. At baseline and week 6, 76% (96/127) had analyzable serial 177Lu SPECT/CT imaging. SPECT total tumor volume (TTV) was reduced between baseline and week 6 in 74% (71/96; median, -193; IQR, -486 to -41). Any increase in SPECT TTV between baseline and week 6 was associated with significantly shorter PSA PFS (hazard ratio, 2.5; 95% CI, 1.5-4.2; P = 0.0008) but not OS. Median PSA PFS in those with an increase in SPECT TTV was 3.7 mo (95% CI, 2.8-6.8), compared with 6.7 mo (95% CI, 5.8-10.6) in those with no increase in SPECT TTV. An increase in SPECT TTV greater than 20% was also associated with PSA PFS (hazard ratio, 1.9; 95% CI, 1.2-3.0; P = 0.008) but less significantly than any change in SPECT TTV. There was a significant difference in PSA PFS between patients with both increased PSA and SPECT TTV and patients with reduced SPECT TTV and PSA (median, 2.8 vs. 9.0 mo; P < 0.0001). Conclusion: Increasing PSMA SPECT TTV on quantitative 177Lu SPECT/CT predicts short progression-free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify 177Lu-PSMA therapy.

Individualised dosimetry and safety of SIRT for intrahepatic cholangiocarcinoma.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of selective internal radiation therapy (SIRT) with 90Y resin microspheres for the treatment of Intrahepatic Cholangiocarcinoma (ICC). A total of 23 SIRT procedures from 18 ICC subjects were analysed to determine a lesion-based dose/response relationship with absorbed dose measures from 90Y PET and metabolic response as measured on [18F]FDG PET. Average absorbed dose (Davg), minimum dose to 70% of the volume (D70), volume receiving at least 50 Gy (V50), biological effective dose (BED) and equivalent uniform dose (EUD), were compared to changes in metabolic volume, maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Dose to normal liver was assessed with changes in liver uptake rate as measured with [99mTc]mebrofenin scintigraphy for a cohort of 20 subjects with primary liver malignancy (12 ICC, 8 hepatocellular carcinoma (HCC)). RESULTS: Thirty-four lesions were included in the analysis. A relationship was found between metabolic response and both Davg and EUD similar to that seen previously in metastatic colorectal cancer (mCRC), albeit trending towards a lower response plateau. Both dose and SUV coefficient of variation within the lesion (CoVdose and CoVSUV), baseline TLG and EUD were found to be mildly significant predictors of response. No strong correlation was seen between normal liver dose and change in [99mTc]mebrofenin liver uptake rate; low baseline uptake rate was not indicative of declining function following SIRT, and no subjects dropped into the 'poor liver function' category. CONCLUSIONS: ICC lesions follow a similar dose-response trend as mCRC, however, despite high lesion doses a full metabolic response was rarely seen. The CoV of lesion dose may have a significant bearing on response, and EUD correlated more tightly with metabolic response compared to Davg. SIRT in primary liver malignancy appears safe in terms of not inducing a clinically significant decline in liver function, and poor baseline uptake rate is not predictive of a reduction in function post SIRT.

Overlooked potential of positrons in cancer therapy.

Positron (ß+) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a ß+ emitter fluorine-18 (18F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, 18F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of ß+ emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of ß+ emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of 18F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for ß+ emitters. These results may also have implications for emerging cancer theranostic strategies, where ß+ emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.

Quantitative PET in the 2020s: a roadmap.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

Performance evaluation of quantitative SPECT/CT using NEMA NU 2 PET methodology.

Although PET is routinely evaluated using NEMA NU2 as standard in the clinic, standard methodology for evaluating the performance of quantitative SPECT systems has not been established. In this study, the quantitative performance of the Symbia Intevo SPECT/CT was evaluated for two common isotopes (99mTc, 177Lu) and benchmarked against the performance of a PET/CT. A further aim was to demonstrate the utility of adapting NEMA NU2 PET measurements to SPECT. In addition, dead-time and resolution recovery were evaluated to provide more complete system evaluations. Spatial resolution of the SPECT system at 1 cm from the center in the transverse direction was 13.1 mm and 22.4 mm for 99mTc and 177Lu respectively, compared with 4.3 mm (18F) and 5.8 mm (68Ga) for PET. Sensitivity at the center of the FoV was 119 cps MBq-1 and 48 cps MBq-1 (99mTc, 177Lu) for SPECT and 9632 cps MBq-1 and 8216 cps MBq-1 (18F, 68Ga) for PET. Scatter fraction was 0.25 and 0.36 (99mTc, 77Lu) for SPECT and 0.32 and 0.29 (18F, 68Ga) for PET. Contrast recovery coefficient in the largest spheres was 0.79 and 0.65 (99mTc, 177Lu) for SPECT, 1.00 and 0.97 (18F, 68Ga) for PET and the background variability was 2.7%, 6.5% (99mTc, 177Lu), 1.5% and 1.6% (18F, 68Ga), respectively. Partial volume effect was evaluated using the NEMA IQ phantom with six sphere inserts (diameter: 37 mm, 28 mm, 22 mm, 17 mm, 13 mm and 10 mm). Full contrast recovery was reached with the 17 mm for 18F, while SPECT did not reach full recovery for any sphere. Count rate losses were 2% for 99mTc at 1 GBq and 11% for 177Lu at 8.5 GBq which are well below the typical activities for clinical applications. We concluded NEMA NU2 methodology can be easily adapted to SPECT/CT as a routine quality assurance procedure in the clinic.

The VAMPIRE challenge: A multi-institutional validation study of CT ventilation imaging.

PURPOSE: CT ventilation imaging (CTVI) is being used to achieve functional avoidance lung cancer radiation therapy in three clinical trials (NCT02528942, NCT02308709, NCT02843568). To address the need for common CTVI validation tools, we have built the Ventilation And Medical Pulmonary Image Registration Evaluation (VAMPIRE) Dataset, and present the results of the first VAMPIRE Challenge to compare relative ventilation distributions between different CTVI algorithms and other established ventilation imaging modalities. METHODS: The VAMPIRE Dataset includes 50 pairs of 4DCT scans and corresponding clinical or experimental ventilation scans, referred to as reference ventilation images (RefVIs). The dataset includes 25 humans imaged with Galligas 4DPET/CT, 21 humans imaged with DTPA-SPECT, and 4 sheep imaged with Xenon-CT. For the VAMPIRE Challenge, 16 subjects were allocated to a training group (with RefVI provided) and 34 subjects were allocated to a validation group (with RefVI blinded). Seven research groups downloaded the Challenge dataset and uploaded CTVIs based on deformable image registration (DIR) between the 4DCT inhale/exhale phases. Participants used DIR methods broadly classified into B-splines, Free-form, Diffeomorphisms, or Biomechanical modeling, with CT ventilation metrics based on the DIR evaluation of volume change, Hounsfield Unit change, or various hybrid approaches. All CTVIs were evaluated against the corresponding RefVI using the voxel-wise Spearman coefficient rS , and Dice similarity coefficients evaluated for low function lung ( DSClow ) and high function lung ( DSChigh ). RESULTS: A total of 37 unique combinations of DIR method and CT ventilation metric were either submitted by participants directly or derived from participant-submitted DIR motion fields using the in-house software, VESPIR. The rS and DSC results reveal a high degree of inter-algorithm and intersubject variability among the validation subjects, with algorithm rankings changing by up to ten positions depending on the choice of evaluation metric. The algorithm with the highest overall cross-modality correlations used a biomechanical model-based DIR with a hybrid ventilation metric, achieving a median (range) of 0.49 (0.27-0.73) for rS , 0.52 (0.36-0.67) for DSClow , and 0.45 (0.28-0.62) for DSChigh . All other algorithms exhibited at least one negative rS value, and/or one DSC value less than 0.5. CONCLUSIONS: The VAMPIRE Challenge results demonstrate that the cross-modality correlation between CTVIs and the RefVIs varies not only with the choice of CTVI algorithm but also with the choice of RefVI modality, imaging subject, and the evaluation metric used to compare relative ventilation distributions. This variability may arise from the fact that each of the different CTVI algorithms and RefVI modalities provides a distinct physiologic measurement. Ultimately this variability, coupled with the lack of a "gold standard," highlights the ongoing importance of further validation studies before CTVI can be widely translated from academic centers to the clinic. It is hoped that the information gleaned from the VAMPIRE Challenge can help inform future validation efforts.

SPECT V/Q in Lung Cancer Radiotherapy Planning.

Curative-intent lung cancer radiation therapy either alone (RT) or combined with immuno-chemotherapy is associated with potential risk of serious radiation-induced lung injury. This review provides a summary of the role of SPECT ventilation perfusion (V/Q) imaging as an emerging adjunct to lung cancer RT planning and treatment dosimetry. Denoted "functional lung avoidance RT" it is hypothesized that preferential dosimetric avoidance of physiologically functional lung may reduce the frequency of radiation-induced lung injury. SPECT V/Q imaging datasets available during the planning process allows the prioritization (or "personalization') of RT dose to minimize the volume of functional lung probabilistically exposed to injurious radiation dose. Selective escalation of target dose and adaptive planning and replanning is also enabled. The emergent importance of the tumor-lung microenvironment and its biologic relationship to local immune effectors in lung cancer provides further incentive to individualize RT planning and delivery. This review examines important normal tissue dosimetric constraints that are part of current standards-of-care and the new dosimetric parameters associated with functional lung avoidance RT. SPECT V/Q has been a valuable tool in investigating the feasibility and efficacy of functional lung avoidance RT but is yet to become main stream due to the lack of large clinical trials. It is encouraging however that functional lung avoidance is feasible in RT dose-target delineation and some of the more promising studies are discussed.

Feasibility and accuracy of single time point imaging for renal dosimetry following 177Lu-DOTATATE ('Lutate') therapy.

BACKGROUND: This study aims to assess both feasibility and accuracy of renal dosimetry imaging protocols in patients receiving Lutate therapy for neuroendocrine tumours (NETs), when data acquisition over multiple days is not possible on all cycles. METHOD: Patients who had received a full 4 cycles of Lutate therapy with complete imaging at each cycle were included. Imaging consisted of quantitative SPECT/CT of the kidneys at 4, 24 and 96-120 h post injection. Renal absorbed dose was calculated for each data set, and in addition, five alternative methods were explored for comparison. Method 1: a patient average clearance time (t1/2 average) derived from the first half of contributing patient data was used to estimate absorbed dose for subsequent patients based on 4 h imaging alone; method 2: t1/2 average was applied to subsequent patients on 24 h imaging alone; method 3: a patient-specific clearance rate (t1/2 patient) was determined from complete image data of cycle 1 and applied subsequently to remaining cycles using 4 h image data alone; method 4: t1/2 patient was applied to 24 h imaging alone in subsequent cycles; method 5: the 120 h data was estimated on subsequent cycles based on the cycle 1 fraction of injected activity (%IA) at 24 and 120 h. RESULTS: Twenty treatments from 18 patients, resulting in 80 cycles of therapy, were analysed. The measured average renal absorbed dose per cycle of treatment was 0.38 ± 0.19 Gy/GBq when derived from full imaging data. The use of t1/2 average applied to a single time point led to large deviations of dose estimates from true values (on average 59% and 30%, when using 4 h data and 24 h data, respectively). The use of complete image data on cycle 1 and the derivation of t1/2 patient led to improved dose estimates, with an average deviation from true values of 13% and 2% when using 4 h data only and 24 h data only, respectively. The use of a 120 h %IA derived from cycle 1 led to an average deviation from true dose estimates of 14%. CONCLUSION: In instances where demands on both patients and facilities make multiple time point data acquisition impractical, renal dosimetry is best derived through complete imaging at cycle 1 only followed by a single 24 h imaging time point on subsequent cycles, assuming no significant changes in renal function during the time course of therapy.

A Comparison of 2D and 3D Kidney Absorbed Dose Measures in Patients Receiving 177Lu-DOTATATE.

OBJECTIVES: To investigate and compare quantitative accuracy of kidney absorbed dose measures made from both 2D and 3D imaging in patients receiving 177Lu-DOTATATE (Lutate) for treatment of neuroendocrine tumours (NETs). METHODS: Patients receiving Lutate therapy underwent both whole body planar imaging and SPECT/CT imaging over the kidneys at time points 0.5, 4, 24, and 96-120 hours after injection. Planar data were corrected for attenuation using transmission data, and were converted to units of absolute activity via two methods, using either a calibration standard in the field of view or relative to pre-voiding image total counts. Hand drawn regions of interest were used to generate time activity curves and kidney absorbed dose estimates in OLINDA-EXM. Fully quantitative SPECT data were generated using CT-derived corrections for both scatter and attenuation, before correction for dead time and application of a camera specific sensitivity factor to convert data to units of absolute activity. Volumes of interest were defined for kidney using the co-registered x-ray CT, before time activity curves and absorbed dose measures were generated in OLINDA-EXM, both with and without corrections made to the model for patient specific kidney volumes. Quantitative SPECT data were also used to derive dose maps through dose kernel convolution (DKC), which was treated as the gold standard. RESULTS: A total of 50 studies were analysed, corresponding to various cycles of treatment from 21 patients. Planar absorbed dose estimates were consistently higher than SPECT derived estimates by, on average, a factor of 3. CONCLUSION: Quantitative SPECT is considered the gold standard approach for organ specific dosimetry however often relies on in house software. As such planar methods for estimating absorbed dose are much more widely available, and in particular, are often the only source of reference in previously published data. For the case of Lutate dosimetry, planar measures may lead to a three-fold increase in measures of kidney absorbed dose.

CT ventilation imaging derived from breath hold CT exhibits good regional accuracy with Galligas PET.

BACKGROUND AND PURPOSE: CT ventilation imaging (CTVI) derived from four dimensional CT (4DCT) has shown only moderate spatial accuracy in humans due to 4DCT image artefacts. Here we assess the accuracy of an improved CTVI using high quality exhale/inhale breath-hold CT (BHCT). MATERIALS AND METHODS: Eighteen lung cancer patients underwent exhale/inhale BHCT, 4DCT and Galligas PET ventilation scans in a single imaging session. For each BHCT and 4DCT scan, we performed deformable image registration (DIR) between the inhale and exhale phase images to quantify ventilation using three published metrics: (i) breathing induced lung density change, CTVIDIR-HU (ii) breathing induced volume change CTVIDIR-Jac and (iii) the regional air-tissue product, CTVIHU Spatial accuracy was reported as the voxel-wise Spearman correlation r between CTVI and Galligas PET. RESULTS: For BHCT-based CTVIs (N = 16), the CTVIDIR-HU, CTVIDIR-Jac and CTVIHU methods yielded mean (range) r values of 0.67 (0.52-0.87), 0.57 (0.18-0.77) and 0.49 (0.14-0.75) respectively. By comparison the 4DCT-based CTVIs (n = 14) had values of 0.32 (-0.04 to 0.51), 0.16 (-0.31 to 44) and 0.49 (0.20-0.77) respectively. CONCLUSIONS: High quality CT imaging is a key requirement for accurate CT ventilation imaging. The use of exhale/inhale BHCT can improve the accuracy of CTVI for human subjects.

Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance.

Background: PET scans using FDG and somatostatin receptor imaging agents have both been used to study neuroendocrine tumours. Most reports have documented the sensitivity and specificity of each radiopharmaceutical independently, and even suggested the superiority of one over the other for different grades of disease. Aim: The aim of this work was to develop a grading scheme that describes the joint results of both the FDG and somatostatin receptor imaging PET scans in staging subjects with neuroendocrine tumours in a single combined parameter. The grading scheme that has been developed is referred to as the NETPET grade. Methods: This is a retrospective study which assessed subjects who had both FDG and somatostatin receptor PET imaging at our institution within 31 days of each other. The NETPET grade was assigned by experienced nuclear medicine physicians and compared with other clinical data such as WHO grade and overall survival. Results: In the period 2011-2015 we were able to recruit 62 subjects with histologically proven metastatic neuroendocrine tumour for review. The NETPET grade incorporating both the FDG and somatostatin receptor imaging results was significantly correlated with overall survival by univariate analysis (p=0.0018), whereas in this cohort the WHO grade at the time of diagnosis did not correlate with survival. Conclusions: The NETPET grade has promise as a prognostic imaging biomarker in neuroendocrine tumours. It permits the capturing of the complexity of dual radiotracer imaging in a single parameter which describes the subjects' disease and is readily amenable to use in patient management and further research.

(68)Ga PET Ventilation and Perfusion Lung Imaging-Current Status and Future Challenges.

Gallium-68 ((68)Ga) is a positron-emitting radionuclide suitable for positron emission tomography (PET) imaging that has a number of convenient features-it has a physical half life of 68 minutes, it is generator produced at the PET facility and needs no local cyclotron, and being a radiometal is able to be chelated to a number of useful molecules for diagnostic imaging with PET. (68)Ga has recently been investigated as a radiotracer for ventilation and perfusion (V/Q) lung imaging. It is relatively easy to produce both V/Q radiopharmaceuticals labeled with (68)Ga for PET studies, it offers higher spatial resolution than equivalent SPECT studies, the short half life allows for multiple (repeated) scans on the same day, and low amounts of radiotracer can be used thus limiting the radiation dose to the subject. In the usual clinical setting requiring a V/Q scan, that of suspected pulmonary embolism, the role of (68)Ga V/Q PET may be limited from a logistical perspective, however, in nonacute applications such as lung function evaluation, radiotherapy treatment planning, and respiratory physiology investigations it would appear to be an ideal modality to employ.

Measurement of preoperative lobar lung function with computed tomography ventilation imaging: progress towards rapid stratification of lung cancer lobectomy patients with abnormal lung function.

OBJECTIVES: In lung cancer preoperative evaluation, functional lung imaging is commonly used to assess lobar function. Computed tomography ventilation (CT-V) imaging is an emerging lung function imaging modality. We compared CT-V imaging assessment of lobar function and its prediction of postoperative lung function to that achieved by (i) positron emission tomography ventilation (PET-V) imaging and (ii) the standard anatomical segment counting (ASC) method. We hypothesized (i) that CT-V and PET-V have similar relative lobar function and (ii) that functional imaging and anatomic assessment (ASC) yield different predicted postoperative (ppo) lung function and therefore could change clinical management. METHODS: In this proof-of-concept study, 11 patients were subjected to pulmonary function tests, CT-V and PET-V imaging. The Bland-Altman plot, Pearson's correlation and linear regression analysis were used to assess the agreement between the CT-V-, PET-V- and ASC-based quantification of lobar function and in the ppo lung function. RESULTS: CT-V and PET-V imaging demonstrated strong correlations in quantifying relative lobar function (r = 0.96; P < 0.001). A Wilcoxon-signed rank test showed no significant difference in the lobar function estimates between the two imaging modalities (P = 0.83). The Bland-Altman plot also showed no significant differences. The correlation between ASC-based lobar function estimates with ventilation imaging was low, r < 0.45; however, the predictions of postoperative lung function correlated strongly between all three methods. CONCLUSIONS: The assessment of lobar function from CT-V imaging correlated strongly with PET-V imaging, but had low correlations with ASC. CT-V imaging may be a useful alternative method in preoperative evaluation for lung cancer patients.

Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis.

BACKGROUND: Functional gastrointestinal symptoms such as abdominal pain, bloating, distension, constipation, diarrhea and flatulence have been noted in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The diversity of symptoms has meant that finding an effective treatment has been challenging with most treatments alleviating only the primary symptom. A novel treatment option for IBS and IBD currently generating much excitement is the low fermentable, oligo-, di-, mono-saccharides and polyol (FODMAP) diet. The aim of this meta-analysis was to determine the evidence of the efficacy of such a diet in the treatment of functional gastrointestinal symptoms. METHODS: Electronic databases were searched through to March 2015 to identify relevant studies. Pooled odds ratios (ORs) and 95 % confidence intervals were calculated for the effect of a low FODMAP diet on the reduction in IBS [Symptoms Severity Score (SSS)] score and increase in IBS quality of life (QOL) score for both randomized clinical trials (RCTs) and non-randomized interventions using a random-effects model. RESULTS: Six RCTs and 16 non-randomized interventions were included in the analysis. There was a significant decrease in IBS SSS scores for those individuals on a low FODMAP diet in both the RCTs (OR 0.44, 95 % CI 0.25-0.76; I (2) = 35.52, p = 0.00) and non-randomized interventions (OR 0.03, 95 % CI 0.01-0.2; I (2) = 69.1, p = 0.02). In addition, there was a significant improvement in the IBS-QOL score for RCTs (OR 1.84, 95 % CI 1.12-3.03; I (2) = 0.00, p = 0.39) and for non-randomized interventions (OR 3.18, 95 % CI 1.60-6.31; I (2) = 0.00, p = 0.89). Further, following a low FODMAP diet was found to significantly reduce symptom severity for abdominal pain (OR 1.81, 95 % CI 1.13-2.88; I (2) = 0.00, p = 0.56), bloating (OR 1.75, 95 % CI 1.07-2.87; I (2) = 0.00, p = 0.45) and overall symptoms (OR 1.81, 95 % CI 1.11-2.95; I (2) = 0.00, p = 0.4) in the RCTs. In the non-randomized interventions similar findings were observed. CONCLUSION: The present meta-analysis supports the efficacy of a low FODMAP diet in the treatment of functional gastrointestinal symptoms. Further research should ensure studies include dietary adherence, and more studies looking at greater number of patients and long-term adherence to a low FODMAP diet need to be conducted.

The Nano-X Linear Accelerator: A Compact and Economical Cancer Radiotherapy System Incorporating Patient Rotation.

Rapid technological improvements in radiotherapy delivery results in improved outcomes to patients, yet current commercial systems with these technologies on board are costly. The aim of this study was to develop a state-of-the-art cancer radiotherapy system that is economical and space efficient fitting with current world demands. The Nano-X system is a compact design that is light weight combining a patient rotation system with a vertical 6 MV fixed beam. In this paper, we present the Nano-X system design configuration, an estimate of the system dimensions and its potential impact on shielding cost reductions. We provide an assessment of implementing such a radiotherapy system clinically, its advantages and disadvantages compared to a compact conventional gantry rotating linac. The Nano-X system has several differentiating features from current radiotherapy systems, it is [1] compact and therefore can fit into small vaults, [2] light weight, and [3] engineering efficient, i.e., it rotates a relatively light component and the main treatment delivery components are not under rotation (e.g., DMLCs). All these features can have an impact on reducing the costs of the system. In terms of shielding requirements, leakage radiation was found to be the dominant contributor to the Nano-X vault and as such no primary shielding was necessary. For a low leakage design, the Nano-X vault footprint and concrete volume required is 17 m2 and 35 m3 respectively, compared to 54 m2 and 102 m3 for a conventional compact linac vault, resulting in decreased costs in shielding. Key issues to be investigated in future work are the possible patient comfort concerns associated with the patient rotation system, as well as the magnitude of deformation and subsequent adaptation requirements.

A study of the native cell wall structures of the marine alga Ventricaria ventricosa (Siphonocladales, Chlorophyceae) using atomic force microscopy.

A substantial proportion of the architecture of the plant cell wall remains unknown with a few cell wall models being proposed. Moreover, even less is known about the green algal cell wall. Techniques that allow direct visualization of the cell wall in as near to its native state are of importance in unravelling the spatial arrangement of cell wall structures and hence in the development of cell wall models. Atomic force microscopy (AFM) was used to image the native cell wall of living cells of Ventricaria ventricosa (V. ventricosa) at high resolution under physiological conditions. The cell wall polymers were identified mainly qualitatively via their structural appearance. The cellulose microfibrils (CMFs) were easily recognizable and the imaging results indicate that the V. ventricosa cell wall has a cross-fibrillar structure throughout. We found the native wall to be abundant in matrix polysaccharides existing in different curing states. The soft phase matrix polysaccharides susceptible by the AFM scanning tip existed as a glutinous fibrillar meshwork, possibly incorporating both the pectic- and hemicellulosic-type substances. The hard phase matrix producing clearer images, revealed coiled fibrillar structures associated with CMFs, sometimes being resolved as globular structures by the AFM tip. The coiling fibrillar structures were also seen in the images of isolated cell wall fragments. The mucilaginous component of the wall was discernible from the gelatinous cell wall matrix as it formed microstructural domains over the surface. AFM has been successful in imaging the native cell wall and revealing novel findings such as the 'coiling fibrillar structures' and cell wall components which have previously not been seen, that is, the gelatinous matrix phase.