The optimal balance between quality and efficiency in proton radiography imaging technique at various proton beam energies: A Monte Carlo study.

Proton radiography is a novel imaging modality that allows direct measurement of the proton energy loss in various tissues. Currently, due to the conversion of so-called Hounsfield units from X-ray Computed Tomography (CT) into relative proton stopping powers (RPSP), the uncertainties of RPSP are 3-5% or higher, which need to be minimized down to 1% to make the proton treatment plans more accurate. In this work, we simulated a proton radiography system, with position-sensitive detectors (PSDs) and a residual energy detector (RED). The simulations were built using Geant4, a Monte Carlo simulation toolkit. A phantom, consisting of several materials was placed between the PSDs of various Water Equivalent Thicknesses (WET), corresponding to an ideal detector, a gaseous detector, silicon and plastic scintillator detectors. The energy loss radiograph and the scattering angle distributions of the protons were studied for proton beam energies of 150MeV, 190MeV and 230MeV. To improve the image quality deteriorated by the multiple Coulomb scattering (MCS), protons with small angles were selected. Two ways of calculating a scattering angle were considered using the proton's direction and position. A scattering angle cut of 8.7mrad was applied giving an optimal balance between quality and efficiency of the radiographic image. For the three proton beam energies, the number of protons used in image reconstruction with the direction method was half the number of protons kept using the position method.

Breast cancer and fat grafting: efficacy, safety and complications-a systematic review.

Autologous fat grafting (AFG) or lipofilling is nowadays a popular technique for breast reconstruction after breast cancer surgery. There is debate regarding the oncological safety and risks of this procedure in breast cancer patients. A systematic review of the literature published between January first 1995 and October first 2016 was conducted regarding the efficacy, safety and complications of this technique in breast cancer patients after their cancer treatment. The databases PubMed, Science Direct and Thomson Reuters Web of Science were used to search for qualified articles. Inclusion criteria were women with a personal history of breast cancer and at least one lipofilling procedure. Only studies containing a minimum of 20 patients were included in this systematic review. The search yielded a total of 23 suitable articles: 18 case series, 4 retrospective cohort studies and one prospective cohort study. The systematic review encompassed a total of 2419 patients. Medical imaging was used in the majority of the studies to assess the follow-up. Mammography was the most popular technique (65.2%), followed by ultrasound (47.8%) and MRI (30.4%). The prevalence of complications was the following: fat necrosis in 5.31%, benign lesions, like cysts or calcifications in 8.78%, infections in 0.96% and local cancer recurrence in 1.69%. AFG or lipofilling appears to be an oncological safe technique with a low morbidity in women with a history of breast cancer. In order to have a better understanding and evidence of the oncological safety a randomised controlled trial is urgently needed. We further recommend that all AFG be registered in the cancer register.

Contrast-enhanced spectral mammography in recalls from the Dutch breast cancer screening program: validation of results in a large multireader, multicase study.

OBJECTIVES: Contrast-enhanced spectral mammography (CESM) is a promising problem-solving tool in women referred from a breast cancer screening program. We aimed to study the validity of preliminary results of CESM using a larger panel of radiologists with different levels of CESM experience. METHODS: All women referred from the Dutch breast cancer screening program were eligible for CESM. 199 consecutive cases were viewed by ten radiologists. Four had extensive CESM experience, three had no CESM experience but were experienced breast radiologists, and three were residents. All readers provided a BI-RADS score for the low-energy CESM images first, after which the score could be adjusted when viewing the entire CESM exam. BI-RADS 1-3 were considered benign and BI-RADS 4-5 malignant. With this cutoff, we calculated sensitivity, specificity and area under the ROC curve. RESULTS: CESM increased diagnostic accuracy in all readers. The performance for all readers using CESM was: sensitivity 96.9 % (+3.9 %), specificity 69.7 % (+33.8 %) and area under the ROC curve 0.833 (+0.188). CONCLUSION: CESM is superior to conventional mammography, with excellent problem-solving capabilities in women referred from the breast cancer screening program. Previous results were confirmed even in a larger panel of readers with varying CESM experience. KEY POINTS: • CESM is consistently superior to conventional mammography • CESM increases diagnostic accuracy regardless of a reader's experience • CESM is an excellent problem-solving tool in recalls from screening programs.

Short-lived positron emitters in beam-on PET imaging during proton therapy.

The only method for in vivo dose delivery verification in proton beam radiotherapy in clinical use today is positron emission tomography (PET) of the positron emitters produced in the patient during irradiation. PET imaging while the beam is on (so called beam-on PET) is an attractive option, providing the largest number of counts, the least biological washout and the fastest feedback. In this implementation, all nuclides, independent of their half-life, will contribute. As a first step towards assessing the relevance of short-lived nuclides (half-life shorter than that of (10)C, T1/2 = 19 s) for in vivo dose delivery verification using beam-on PET, we measured their production in the stopping of 55 MeV protons in water, carbon, phosphorus and calcium The most copiously produced short-lived nuclides and their production rates relative to the relevant long-lived nuclides are: (12)N (T1/2 = 11 ms) on carbon (9% of (11)C), (29)P (T1/2 = 4.1 s) on phosphorus (20% of (30)P) and (38m)K (T1/2 = 0.92 s) on calcium (113% of (38g)K). No short-lived nuclides are produced on oxygen. The number of decays integrated from the start of an irradiation as a function of time during the irradiation of PMMA and 4 tissue materials has been determined. For (carbon-rich) adipose tissue, (12)N dominates up to 70 s. On bone tissue, (12)N dominates over (15)O during the first 8-15 s (depending on carbon-to-oxygen ratio). The short-lived nuclides created on phosphorus and calcium provide 2.5 times more beam-on PET counts than the long-lived ones produced on these elements during a 70 s irradiation. From the estimated number of (12)N PET counts, we conclude that, for any tissue, (12)N PET imaging potentially provides equal to superior proton range information compared to prompt gamma imaging with an optimized knife-edge slit camera. The practical implementation of (12)N PET imaging is discussed.

Spectra of clinical CT scanners using a portable Compton spectrometer.

PURPOSE: Spectral information of the output of x-ray tubes in (dual source) computer tomography (CT) scanners can be used to improve the conversion of CT numbers to proton stopping power and can be used to advantage in CT scanner quality assurance. The purpose of this study is to design, validate, and apply a compact portable Compton spectrometer that was constructed to accurately measure x-ray spectra of CT scanners. METHODS: In the design of the Compton spectrometer, the shielding materials were carefully chosen and positioned to reduce background by x-ray fluorescence from the materials used. The spectrum of Compton scattered x-rays alters from the original source spectrum due to various physical processes. Reconstruction of the original x-ray spectrum from the Compton scattered spectrum is based on Monte Carlo simulations of the processes involved. This reconstruction is validated by comparing directly and indirectly measured spectra of a mobile x-ray tube. The Compton spectrometer is assessed in a clinical setting by measuring x-ray spectra at various tube voltages of three different medical CT scanner x-ray tubes. RESULTS: The directly and indirectly measured spectra are in good agreement (their ratio being 0.99) thereby validating the reconstruction method. The measured spectra of the medical CT scanners are consistent with theoretical spectra and spectra obtained from the x-ray tube manufacturer. CONCLUSIONS: A Compton spectrometer has been successfully designed, constructed, validated, and applied in the measurement of x-ray spectra of CT scanners. These measurements show that our compact Compton spectrometer can be rapidly set-up using the alignment lasers of the CT scanner, thereby enabling its use in commissioning, troubleshooting, and, e.g., annual performance check-ups of CT scanners.

The role of magnetic resonance imaging in assessing residual disease and pathologic complete response in breast cancer patients receiving neoadjuvant chemotherapy: a systematic review.

OBJECTIVES: This systematic review aimed to assess the role of magnetic resonance imaging (MRI) in evaluating residual disease extent and the ability to detect pathologic complete response (pCR) after neoadjuvant chemotherapy for invasive breast cancer. METHODS: PubMed, the Cochrane Library, MEDLINE, and Embase databases were searched for relevant studies published until 1 July 2012. After primary selection, two reviewers independently assessed the content of each eligible study using a standardised extraction form and pre-defined inclusion and exclusion criteria. RESULTS: A total of 35 eligible studies were selected. Correlation coefficients of residual tumour size assessed by MRI and pathology were good, with a median value of 0.698. Reported sensitivity, specificity, positive predictive value and negative predictive value for predicting pCR with MRI ranged from 25 to 100 %, 50-97 %, 47-73 % and 71-100 %, respectively. Both overestimation and underestimation were observed. MRI proved more accurate in determining residual disease than physical examination, mammography and ultrasound. Diagnostic accuracy of MRI after neoadjuvant chemotherapy could be influenced by treatment regimen and breast cancer subtype. CONCLUSIONS: Breast MRI accuracy for assessing residual disease after neoadjuvant chemotherapy is good and surpasses other diagnostic means. However, both overestimation and underestimation of residual disease extent could be observed. MAIN MESSAGES: • Breast MRI accuracy for assessing residual disease is good and surpasses other diagnostic means. • Correlation coefficients of residual tumour size assessed by MRI and pathology were considered good. • However, both overestimation and underestimation of residual disease were observed. • Diagnostic accuracy of MRI seems to be affected by treatment regimen and breast cancer subtype.

Pre-treatment differences and early response monitoring of neoadjuvant chemotherapy in breast cancer patients using magnetic resonance imaging: a systematic review.

OBJECTIVES: To assess whether magnetic resonance imaging (MRI) can identify pre-treatment differences or monitor early response in breast cancer patients receiving neoadjuvant chemotherapy. METHODS: PubMed, Cochrane library, Medline and Embase databases were searched for publications until January 1, 2012. After primary selection, studies were selected based on predefined inclusion/exclusion criteria. Two reviewers assessed study contents using an extraction form. RESULTS: In 15 studies, which were mainly underpowered and of heterogeneous study design, 31 different parameters were studied. Most frequently studied parameters were tumour diameter or volume, K(trans), K(ep), V(e), and apparent diffusion coefficient (ADC). Other parameters were analysed in only two or less studies. Tumour diameter, volume, and kinetic parameters did not show any pre-treatment differences between responders and non-responders. In two studies, pre-treatment differences in ADC were observed between study groups. At early response monitoring significant and non-significant changes for all parameters were observed for most of the imaging parameters. CONCLUSIONS: Evidence on distinguishing responders and non-responders to neoadjuvant chemotherapy using pre-treatment MRI, as well as using MRI for early response monitoring, is weak and based on underpowered study results and heterogeneous study design. Thus, the value of breast MRI for response evaluation has not yet been established. KEY POINTS: Few well-validated pre-treatment MR parameters exist that identify responders and non-responders. Eligible studies showed heterogeneous study designs which hampered pooling of data. Confounders and technical variations of MRI accuracy are not studied adequately. Value of MRI for response evaluation needs to be established further.

Ground-state proton decay of 69Br and implications for the 68Se astrophysical rapid proton-capture process waiting point.

We report on the first direct measurement of the proton separation energy for the proton-unbound nucleus (69)Br. Bypassing the (68)Se waiting point in the rp process is directly related to the 2p-capture rate through (69)Br, which depends exponentially on the proton separation energy. We find a proton separation energy for (69)Br of Sp((69)Br )= -785(-40)(+34) keV; this is less bound compared to previous predictions which have relied on uncertain theoretical calculations. The influence of the extracted proton separation energy on the rp process occurring in type I x-ray bursts is examined within the context of a one-zone burst model.

Geant4 simulations of proton beam transport through a carbon or beryllium degrader and following a beam line.

Monte Carlo simulations based on the Geant4 simulation toolkit were performed for the carbon wedge degrader used in the beam line at the Center of Proton Therapy of the Paul Scherrer Institute (PSI). The simulations are part of the beam line studies for the development and understanding of the GANTRY2 and OPTIS2 treatment facilities at PSI, but can also be applied to other beam lines. The simulated stopping power, momentum distributions at the degrader exit and beam line transmission have been compared to accurate benchmark measurements. Because the beam transport through magnetic elements is not easily modeled using Geant4a connection to the TURTLE beam line simulation program was made. After adjusting the mean ionization potential of the carbon degrader material from 78 eV to 95 eV, we found an accurate match between simulations and benchmark measurements, so that the simulation model could be validated. We found that the degrader does not completely erase the initial beam phase space even at low degraded beam energies. Using the validation results, we present a study of the usability of beryllium as a degrader material (mean ionization potential 63.7 eV). We found an improvement in the transmission of 30-45%, depending on the degraded beam energy, the higher value for the lower energies.

Diffusion restriction in a superficial breast lesion.

OBJECTIVE: To report the imaging findings of a 22-year-old Asian woman with a freely movable retro-areolar nodule in the right breast, first noticed after a holiday in The Philippines. MATERIAL AND METHODS: We preformed clinical examination, mammography and ultrasound with color Doppler imaging. A differential diagnosis of epidermal inclusion cyst, complex cyst, well demarcated carcinoma and echinococcus cyst was proposed. For further differential diagnosis, a MRI of the breasts was performed on a 1.5 superconducting system, with a bilateral breast coil. T2- and T1 weighted images, followed by axial echo-planar diffusion-weighted MRI (DW-MRI) were performed with b values of 0, 500, and 1000 mm2/s (trace images and ADC maps). RESULTS: The high signal intensity on T2 weighted images confirmed the cystic character of the lesion. The high signal intensity on T1 FS weighted images can be seen in complex cysts and inclusion cysts, but is less likely in an echinococcus cyst. On DW-MRI there is a marked diffusion restriction in the nodule, which can be seen in complex cysts and inclusion cysts. A well demarcated carcinoma is less likely, unless a tumour with a very high cellularity. Because neither carcinoma nor echinococcus cyst could be ruled out, a surgical excision was performed. Pathological examination revealed normal squamous epithelium with stratification and lamellated keratin, consistent with an epidermal inclusion cyst. CONCLUSION: We argue that in selected cases DW-MRI can be useful to narrow the differential diagnosis and notable differentiate epidermal inclusion cysts from echinococcus cysts.

MR mammography is useful in the preoperative locoregional staging of breast carcinomas with extensive intraductal component.

PURPOSE: To determine the role of magnetic resonance (MR) mammography in detection and assessment of extent of tumors with extensive intraductal component (EIC+). MATERIAL AND METHODS: In a prospective study, 233 consecutive women with a suspicious lesion underwent preoperative MR mammography and 209 invasive ductal carcinomas were detected. We studied the prediction of intraductal spread on mammography (MX), ultrasound (US) and MR. We compared the size of the total lesion on MX, US and MR and correlated it with histopathology. Enhancement patterns on MR were described. RESULTS: Of 209 invasive ductal carcinomas, 50 were EIC+ (24%). MX predicted intraductal spread in EIC+ carcinomas in 48.5%, US in 34.2% and MR in 68%. Compared to MX and US, MR was best in assessment of total tumor size. On MR, ductal spread in EIC+ tumors presented as ductal or linear enhancement, long spicules, a regional enhancing area or nodules adjacent to a mass. CONCLUSION: MR had the highest sensitivity to predict intraductal spread and was superior in assessing total tumor size.

Magnetic resonance imaging in breast cancer.

AIM: Due to its high sensitivity, magnetic resonance (MR) mammography is increasingly used as adjunct to mammography and ultrasound. The technique, however, has a relatively limited specificity. Therefore, it may only be used for specific indications. One of the indications is preoperative staging of breast carcinoma. This review serves to give an overview of the studies published on the role of MR in preoperative local staging. METHODS: We reviewed studies of the role of MR mammography in the detection of breast carcinomas and in the assessment of the diameter and extent of carcinomas. We also reviewed published studies on detection of multifocal and multicentric carcinomas that were occult on mammography and ultrasound. Advantages and drawbacks of preoperative MR mammography and the effect on treatment, as reported in different published studies, are described. The review is based on a search of PubMed, using specific terms for the different topics. RESULTS: MR has the highest sensitivity to detect invasive carcinomas and is best in assessment of tumor extent, including detection of multifocal, multicentric and bilateral disease. CONCLUSION: MR mammography is a valuable adjunct to conventional imaging in the preoperative local staging of breast cancer.

Evaluation of the diagnostic value of a computed radiography system by comparison of digital hard copy images with screen-film mammography: results of a prospective clinical trial.

The purpose of the study was to determine prospectively the diagnostic value of a computed radiography (CR) system by comparing mammographic hard copy images with screen-film mammography (SFM). A series of 100 patients, who came for diagnostic investigation, underwent two-view SFM (Lorad M-IV Platinum) and digital mammography with a CR system (AGFA CR system). The images were obtained by double exposure, i.e. same view without removing compression of the corresponding breast. The CR images were processed with dedicated processing for mammography. Six radiologists read sets of SFM and CR images. The primary efficacy parameter was the overall diagnostic value. The secondary efficacy parameters were lesion conspicuity and lesion details (for masses and micro-calcifications), tissue visibility at chest wall and at skin line, axillary details, overall density and sharpness impression and the overall noise impression. These parameters were scored by a 7-point scoring system. "CR non-inferior to SFM" was concluded if the lower confidence interval bound exceeded 80%. The confidence interval for the overall diagnostic value was between 96.4% and 100%. Pooled analysis of the ten features for image quality comparison demonstrated for all but one feature (lesion details of the calcifications) CR non-inferiority to SFM.

Comparison of MRI features of different grades of DCIS and invasive carcinoma of the breast.

The purpose of the study is to compare mammography and magnetic resonance (MR) mammography in detection and assessment of extent, of histologically proven ductal carcinoma in situ (DCIS) and to compare MR features of DCIS, with features of invasive carcinoma. Forty histopathologically proven and MR detected pure DCIS lesions were described and compared with 213 enhancing invasive carcinomas. Histopathological examination revealed 49 pure DCIS, MR detected 40 of them (81.6%). There was a good correlation between diameter measured on mammography, MR and histopathology. MR was able to detect additional foci. Ductal enhancement, a focal area or a mass were perceived in respectively 8 (20%), 8 (20%) and 24 (60%) DCIS and in 0, 6 (2.8%) and 207 (97.2%) invasive lesions. Maximal contrast enhancement after 3 minutes was seen in 60.9% of DCIS and before 3 minutes in 61% of invasive masses. Signal intensity increase of more than 100% was seen in 76.9% of DCIS and in 91.1% of invasive carcinomas. DCIS had a wash out in 53.8% and invasive carcinomas in 65.3%. MR was able to detect 81.6% of DCIS. Diameter prediction was good on mammography and MR mammography. The only MR feature exclusively seen in DCIS was ductal enhancement.

New approach for measuring properties of rp-process nuclei.

A new experimental approach was developed that can reduce the uncertainties in astrophysical rapid proton capture (rp) process calculations due to nuclear data. This approach utilizes neutron removal from a radioactive ion beam to populate the nuclear states of interest. Excited states were deduced by the gamma-decay spectra measured in a semiconductor Ge-detector array. In the first case studied, 33Ar, excited states were measured with uncertainties of several keV. The 2 orders of magnitude improvement in the uncertainty of the level energies resulted in a 3 orders of magnitude improvement in the uncertainty of the calculated 32Cl(p,gamma)33Ar rate that is critical to the modeling of the rp process. This approach has the potential to measure key properties of almost all interesting nuclei on the rp-process path.

Exclusive measurement of quasifree proton-neutron bremsstrahlung.

Data on proton-neutron bremsstrahlung have been obtained from a measurement of the quasifree breakup channel in proton-deuteron bremsstrahlung. This high-precision measurement, with an incident proton energy of 190 MeV, is fully exclusive; i.e., the protons, the neutron, and the photon have been detected. The quasifree differential cross sections obtained are compared with microscopic calculations and calculations based on soft-photon models. There are sizable differences between the models and also between the models and the data obtained for this simple process.

Contrast-enhanced MR imaging of breast lesions and effect on treatment.

PURPOSE: To assess the value of local staging with preoperative magnetic resonance imaging (MRI) in patients with suspect breast lesions and the effect on therapeutic approach. MATERIALS AND METHODS: Two hundred and four consecutive women with suspect breast lesions on clinical examination (CE) and/or mammography (MX) and/or ultrasound (US) underwent preoperative contrast-enhanced MRI. Detection of multifocal, multicentric and bilateral breast cancer by all three imaging modalities was evaluated. Results of preoperative breast MRI were discussed with the treating surgeons. The type of therapeutic change after preoperative MRI was marked on a questionnaire (none, additional fine needle aspiration, core biopsy, open biopsy, wider excision, mastectomy) and considered 'necessary' or 'unnecessary' using final histopathological results as gold standard. RESULTS: In 170 patients, breast cancer was diagnosed. MRI detected 96% of multifocal disease and 95% of multicentric disease, whereas MX depicted 37 and 18%, and US 41 and 9% of them, respectively. All bilateral breast cancers were seen on MRI; both MX and US detected 56%. Findings of more extensive disease and unsuspected multiple breast cancer foci identified on MRI only, changed the therapeutic approach correctly in 30.6% of breast cancer patients. Nine unnecessary wider excisions and three unnecessary FNA/core biopsies were performed because MRI overestimated the number or size of malignant lesions. CONCLUSION: Preoperative breast MRI is an important adjunct to conventional imaging in the loco-regional staging of breast cancer and a useful tool in treatment planning.

Massive infarction of a recurrent phyllodes tumor of the breast: MRI-findings.

We report the imaging findings in an infarcted phyllodes tumor of the breast. A 40-year-old woman presented ten months after surgery for a benign phyllodes tumour with a palpable lump under the scar. We performed clinical examination, mammography, sonography, and MRI. The radiological diagnosis was a postoperative hematoma with granulation tissue. Surgery was performed. Histological diagnosis revealed an infarcted phyllodes tumour. This case illustrates the radiological presentation of a completely infarcted phyllodes tumour. As far as we know, imaging findings of an infarcted phyllodes tumour have not been reported yet.

Preoperative breast MRI in patients with invasive lobular breast cancer.

To investigate the use of MRI in preoperative characterization of invasive lobular breast cancer (ILC) and in detection of multifocal/multicentric disease. We retrospectively reviewed T1-weighted FLASH 3D precontrast and postcontrast MR images together with subtraction images of 26 women with histopathologically proven invasive lobular cancer. Two experienced radiologists described tumor patterns of ILC independently. MR findings of unifocal, multifocal, single quadrant and multiquadrant disease were correlated with results of other imaging techniques and compared with histopathological findings as gold standard. Most ILC presented on MRI as a single spiculated/irregular, inhomogeneous mass (pattern 1, n=12) or as a dominant lesion surrounded by multiple small enhancing foci (pattern 2, n=8). Multiple small enhancing foci with interconnecting enhancing strands (pattern 3) and an architectural distortion (pattern 4) were both described in three cases. There was one case of a focal area of inhomogeneous enhancement (pattern 5) and one normal MR examination (pattern 6). Unifocal and multifocal lesions were identified on MRI in four patients with normal conventional imaging. In nine women, multiple additional lesions or more extensive multiquadrant disease were correctly identified only on MRI. MRI may play an important role in the evaluation of patients with ILC, which is often difficult to diagnose on clinical examination and conventional imaging and more likely occur in multiple sites and in both breasts. However, false-negative MR findings do occur in a small percentage of ILC.