Influence of interfraction motion on margins for radiotherapy of gastric cancer

Objective:

The aim of this study was to evaluate interfraction uncertainties using kilovoltage (kV) radiographs for patients with gastric cancer during chemoradiotherapy and to calculate the planning target volume (PTV) margins.

Methods:

1284 measurements of set-up errors were analysed for treated patients. The measurements of craniocaudal (axis y), laterolateral (axis x) and anteroposterior (axis z) shifts in kV radiographs were performed. Interfraction clinical target volume (CTV)–PTV margins for all directions were calculated using the van Herk formula.

Results:

The main shift for the y-axis was 0.7 mm [standard deviation (SD), ±7.6], for the x-axis was 0.4 mm (SD, ±3.7) and for the z-axis was 0.6 mm (SD, ±3.5). The CTV–PTV margin in the x, y and z directions was 8.3, 15.5 and 8.0 mm, respectively. We observed that the interfractional motion for patients increased approximately 0.0034 cm along the x direction with each subsequent fraction, whereas a 0.0058-cm reduction in length along the y-axis was observed. No time effects for the z direction were noticed.

Conclusion:

According to our experience, a PTV margin of 9 mm along the x-axis, 16 mm along the y-axis and 8 mm along the z direction should be considered in the absence of image-guided radiotherapy.

Advances in knowledge:

This knowledge concerning PTV set-up margins could be particularly useful for centres without a kV on-board imaging system.In the treatment of gastric cancer, local recurrence is a major problem and occurs in 40–65% of the patients treated.^1,2 Radical surgery is the gold-standard therapy,^3,4 yet, still promotes suboptimal survival. Surgery itself provides long-term survival (5-year survival rate) for only 20–30% of patients.⁵ Adjuvant chemoradiotherapy has been provided to produce a reduction in locoregional relapses and an improvement in survival.⁶ A novel gastric cancer treatment strategy consisting of neoadjuvant chemoradiotherapy and surgery demonstrated a high rate of R0 resection, pathological complete response (PCR) and a low level of local recurrences.^7,8 Radiotherapy (RT) has become an important part of gastric cancer treatment. However, the anatomic accuracy of RT depends on the ability of a positioning system to reproduce a patient''s geometry during simulation, CT scanning and treatment procedures, precision in delineation especially can cause better outcomes, which is why the contouring should be completed by two radiation oncologists with a special interest in gastrointestinal malignancies. Accurate patient positioning between and during each fraction of RT is very important for adequate tumour treatment, especially for intensity-modulated radiation therapy (IMRT) of gastric cancer. This type of treatment may reduce the radiation dose to normal adjacent tissue structures surrounding the stomach, such as bowel, the liver, the kidneys, the spinal cord, the heart, the pancreas and the lung. If this procedure is carried out imprecisely there can be a local control reduction. With the introduction of image-guided RT (IGRT), geometric variations such as set-up error and organ motion can be measured and used in correction protocols. This allows a reduction in the additional margins around the clinical target volume (CTV), or the internal tumour volume (ITV), which are added to form the planning target volume (PTV). This procedure may reduce complications and potentially improve local control through dose escalation. There are four types of systems for the correction of patient position during RT: electronic portal imaging devices; an ultrasound system; and kilovoltage and megavoltage cone beam CT (CBCT). Data from these systems permit the accurate measurement of systematic and random set-up errors. The International Commission on Radiation Units and Measurements guidelines require the determination of the PTV. PTV margins have been defined by van Herk et al.⁹ However, results could be different for each calculation. Most studies have used van Herk formula, linking the PTV margin with systematic and random errors. Still, the PTV margin in the case of stomach cancer is not well defined. Scientists from the Princess Margaret Hospital showed that the median interfraction displacement was approximately 6 mm in the craniocaudal (CC) direction and 2 mm in the other directions, and they recommend a minimal internal margin of 1 cm superiorly and inferiorly, 5 mm anteriorly, posteriorly and to the right and left.¹⁰ Other authors^11,12 have recommended a 1-cm addition to the CTV, but there are no calculations to confirm those. Thus, the purpose of the present study was to determine the connection between PTV margins and interfraction motion for our adaptive procedure according to the van Herk formula using calculations. Currently, there are no data concerning the set-up of margin calculations for RT of gastric cancer. Our study could be particularly useful for RT departments with lack of IGRT.     

A planning target volume margin formula for hypofractionated intracranial stereotactic radiotherapy under cone beam CT image guidance with a six-degrees-of-freedom robotic couch and a mouthpiece-assisted mask system: a preliminary study

Objective:

A planning target volume (PTV) margin formula for hypofractionated intracranial stereotactic radiotherapy (SRT) has been proposed under cone beam CT (CBCT) image guidance with a six-degrees-of-freedom (6-DOF) robotic couch.

Methods:

CBCT-based registration using a 6-DOF couch reportedly led to negligibly small systematic positioning errors, suggesting that each in-treatment positioning error during the treatment courses for the patients employing this combination was predominantly caused by a random gaussian process. Under this assumption, an anisotropic PTV margin for each axis was formulated based on a gaussian distribution model. 19 patients with intracranial lesions who underwent additional post-treatment CBCT were consecutively selected, to whom stereotactic hypofractionated radiotherapy was delivered by a linear accelerator equipped with a CBCT imager, a 6-DOF couch and a mouthpiece-assisted mask system. Time-averaged patient-positioning errors during treatment were estimated by comparing the post-treatment CBCT with the reference planning CT images.

Results:

It was suggested that each histogram of the in-treatment positioning error in each axis would approach each single gaussian distribution with a mean of zero. The calculated PTV margins in the x, y and z directions were 0.97, 1.30 and 0.88 mm, respectively.

Conclusion:

The empirical isotropic PTV margin of 2 mm used in our facility for intracranial SRT was consistent with the margin calculated by the proposed gaussian model.

Advances in knowledge:

We have proposed a PTV margin formula for hypofractionated intracranial SRT under CBCT image guidance with a 6-DOF robotic couch.Frameless radiotherapy for treating intracranial lesions has been widely adopted under the guidance of on-board cone beam CT (CBCT) and a mask system with a six-degrees-of-freedom (6-DOF) robotic couch^1–3 or a semi-robotic couch including manual angle adjustments.⁴ Reported maximum registration errors along any Cartesian co-ordinate axis were 0.5 mm for a phantom;¹ and 1.0 or 3.2 mm (mask dependent),² 2.0 ³ and 1.2 mm⁴ for patients. The mean ± standard deviation (SD) along any Cartesian co-ordinate axis was 0.07 ± 0.17 mm for a phantom based on 12 plans and 5 repeated CBCT acquisitions,¹ 0.2 ± 0.4 mm for 10 patients with 6 fractions³ and 0.4 ± 0.3 mm for a phantom and 0.5 ± 0.3 mm for patients including manual couch angle adjustments.⁴ Meyer et al¹ stated that there was no systematic error because they observed a small mean error for their phantom study.Margins between clinical target volumes (CTVs) and planning target volumes (PTVs) are often calculated using a formula proposed by van Herk et al.^5,6 This formula employed two independent statistical models including a patient-to-patient variation model that gives a mean preparation error in all fractions for each patient, and a random error model during treatment delivery owing to random tumour movement. A patient population coverage probability of 90% in a facility was calculated by the patient-to-patient variation model, and the random error model was used to add further margins by increasing penumbra widths. Our intracranial stereotactic radiotherapy (SRT) utilizes an Elekta Synergy® (Elekta AB, Stockholm, Sweden) linear accelerator (linac) equipped with a CBCT imager, XVI and a 6-DOF robotic couch, HexaPOD™ (Elekta AB), which are identical to the system that Meyer et al¹ described. Consequently, our study can be based on the small mean preparation error reported by Meyer et al, and the above margin model may not be applicable. In addition, the previous margin model assumed that the tumour was spherical, and the margin was defined in the radial direction of the spherical co-ordinate system. For example, Guckenberger et al² calculated the PTV margin in the radial direction using registration results for 47 patients with various treatment sites and fixation means, leading to a PTV margin of 1.7 mm that achieved 90% population coverage. Meanwhile, a more accurate margin formula in the Cartesian co-ordinate system that complies with patient couch movements was proposed, in which the margins were anisotropically defined along the x, y and z directions.⁷The purpose of this study was to propose a PTV margin formula as per the Cartesian co-ordinate system for hypofractionated intracranial SRT under CBCT image guidance with a 6-DOF robotic couch.     

Assessment of coincidence and defect sizes in Bankart and Hill–Sachs lesions after anterior shoulder dislocation: a radiological study

Objective:

Bankart and Hill–Sachs lesions are often associated with anterior shoulder dislocation. The MRI technique is sensitive in diagnosing both injuries. The aim of this study was to investigate Bankart and Hill–Sachs lesions with MRI to determine the correlation in occurrence and defect sizes of these lesions.

Methods:

Between 2006 and 2013, 446 patients were diagnosed with an anterior shoulder dislocation and 105 of these patients were eligible for inclusion in the study. All patients were examined using MRI. Bankart lesions were classified as cartilaginous or bony lesions. Hill–Sachs lesions were graded I–III using a modified Calandra classification.

Results:

The co-occurrence of injuries was high [odds ratio (OR) = 11.47; 95% confidence interval (CI) = 3.60–36.52; p < 0.001]. Patients older than 29 years more often presented with a bilateral injury (OR = 16.29; 95% CI = 2.71–97.73; p = 0.002). A correlation between a Bankart lesion and the grade of a Hill–Sachs lesion was found (ρ = 0.34; 95% CI = 0.16–0.49; p < 0.001). Bankart lesions co-occurred more often with large Hill–Sachs lesions (OR = 1.24; 95% CI = 1.02–1.52; p = 0.033).

Conclusion:

If either lesion is diagnosed, the patient is 11 times more likely to have suffered the associated injury. The size of a Hill–Sachs lesion determines the co-occurrence of cartilaginous or bony Bankart lesions. Age plays a role in determining the type of Bankart lesion as well as the co-occurrence of Bankart and Hill–Sachs lesions.

Advances in knowledge:

This study is the first to demonstrate the use of high-quality MRI in a reasonably large sample of patients, a positive correlation of Bankart and Hill–Sachs lesions in anterior shoulder dislocations and an association between the defect sizes.A shoulder dislocation is a traumatic event with an incidence of around 24 per 100 000 in North America.^1,2 Anterior shoulder dislocation is the most common direction, and most patients are male.^1–4 The highest incidence (48 per 100 000) was found between the ages of 20 and 29 years.² Anterior dislocation causes a typical impression fracture on the posterior humeral head, known as a Hill–Sachs lesion.^5,6 The labrum or the glenoid itself may also be damaged; these injuries are known as Bankart lesions.⁷Although Hill–Sachs lesions can be found in 47–100% of all patients with first-time or recurrent shoulder dislocation, a distinction must be drawn between cartilaginous and bony Bankart lesions.^8–13 Cartilaginous lesions occur more often than bony ones.¹⁴ However, Bankart and Hill–Sachs lesions do not necessarily occur simultaneously. In 2006, Widjaja et al¹⁵ reported that, if one of the lesions was identified, the other was 2.67 times as likely to be present. Yet, this result failed to reach statistical significance because of the small sample size. Griffith et al¹⁰ evaluated CT scans and found a weak correlation between glenoidal bone loss and the size of the Hill–Sachs lesion (p = 0.030). However, the more frequently occurring cartilaginous Bankart lesion was not considered in this study.The aim of the present study was to evaluate the association between defect sizes in Hill–Sachs and bony as well as cartilaginous Bankart lesions after anterior shoulder dislocation using MRI. We hypothesized that there exists a higher correlation than previously thought between temporal occurrence and defect size of the lesions. The results of this study should help to improve diagnostic and therapeutic procedures.     

The role of the ADC value in the characterisation of renal carcinoma by diffusion-weighted MRI

The purpose of this study is to evaluate the role of diffusion-weighted imaging (DWI) in combination with T₁ and T₂ weighted MRI for the characterisation of renal carcinoma. The institutional review board approved the study protocols and waived informed consent from all of the patients. 47 patients (32 male and 15 female; age range, 21–85 years; median age, 65 years) who had suspected renal lesions on abdominal CT underwent MRI for further evaluation and characterisation of the lesions from April 2005 to August 2007 in our university hospital. A region of interest was drawn around the tumour area on apparent diffusion coefficient (ADC) maps. Final diagnosis was confirmed by histological examination of surgical specimens from all patients. The ADC value was significantly higher in renal cell carcinoma (RCC) than in transitional cell carcinoma (2.71±2.35 × 10⁻³ mm² s⁻¹ vs 1.61±0.80 × 10⁻³ mm² s⁻¹; p = 0.022). While analysing the histological subtypes of RCC, a significant difference in ADC values between clear cell carcinoma and non-clear cell carcinoma was found (1.59±0.55 × 10⁻³ mm² s⁻¹ vs 6.72±1.85 × 10⁻³ mm² s⁻¹; p = 0.0004). Similarly, ADC values of RCC revealed a significant difference between positive and negative metastatic lesions (1.06±0.38 × 10⁻³ mm² s⁻¹ vs 3.02±2.44 × 10⁻³ mm² s⁻¹; p = 0.0004), whereas intensity on T₁ and T₂ weighted imaging did not reach statistical significance. In conclusion, DWI has clinical value in the characterisation of renal carcinomas and could be applied in clinical practice for their management.Renal cell carcinoma (RCC) is the most common primary malignant tumour of the kidney; it accounts for 2–3% of all adult cancers and is the sixth cause of death by tumour throughout the world. More than 80% of renal cancers that arise in the renal parenchyma are RCC, whereas the majority of renal pelvis cancers are transitional cell carcinomas (TCCs) [1–3]. The three most common subtypes of RCC are (i) clear cell carcinoma, one of the most common types, accounting for 70–80% of cases; (ii) papillary renal cell carcinoma, accounting for about 10–15% of cases; and (iii) chromophobe renal carcinoma, which is the least common, accounting for 5% of all RCCs. The annual rate of RCC diagnosis is increasing as a result of incidental detection by cross-sectional abdominal imaging of patients with suspected abdominal disorders. Increased detection rates carry a favourable prognosis; however, mortality from RCC has not decreased [2–4].Diffusion-weighted imaging (DWI) is frequently used in cranial MRI studies and has shown potential for the characterisation of lesions such as acute cerebral infarctions, intracranial tumours, various infectious diseases and metabolic disorders [5–8]. The role of DWI is limited outside the central nervous system, owing to its inherent extreme sensitivity to motion, such as that related to respiration, peristalsis and artefacts, thus resulting in a high signal to noise ratio. With the development of advanced MR technology and the use of faster robust sequences, better quality has been obtained in abdominal imaging [9]. DWI with high b-values has been reported to have a high sensitivity for depicting malignant disease. Apparent diffusion coefficient (ADC) values of malignant hepatic, ovarian, breast, prostatic, colonic and uterine cervical tumours were lower than those of benign lesions or normal tissue [10–18].Previous studies have suggested that patients with chromophobe and papillary RCC have a better prognosis than patients with clear cell RCC [19]. Accurate characterisation of patients with renal masses is essential to ensure appropriate clinical management, staging and prognosis. The clinical utility of ADC values in kidney disease has been reported: a higher value of ADC was noted in simple renal cysts and renal pelvis of hydronephrotic kidney, whereas a lower value was noted in solid renal tumours and kidneys with chronic and acute renal failure [9, 20–22]. The role of the ADC value in characterising the histological subtypes of renal carcinoma is limited [3, 9]. Therefore, the present study aimed to evaluate the role of DWI in combination with T₁ and T₂ weighted MRI for the differential diagnosis and characterisation of renal carcinoma.     

Diffusion-weighted imaging in the head and neck region: usefulness of apparent diffusion coefficient values for characterization of lesions

PURPOSE

We aimed to evaluate the role of apparent diffusion coefficient (ADC) values calculated from diffusion-weighted imaging for head and neck lesion characterization in daily routine, in comparison with histopathological results.

METHODS

Ninety consecutive patients who underwent magnetic resonance imaging (MRI) at a university hospital for diagnosis of neck lesions were included in this prospective study. Diffusion-weighted echo-planar MRI was performed on a 1.5 T unit with b factor of 0 and 1000 s/mm² and ADC maps were generated. ADC values were measured for benign and malignant whole lesions seen in daily practice.

RESULTS

The median ADC value of the malignant tumors and benign lesions were 0.72×10⁻³ mm²/s, (range, 0.39–1.51×10⁻³ mm²/s) and 1.17×10⁻³ mm²/s, (range, 0.52–2.38×10⁻³ mm²/s), respectively, with a significant difference between them (P < 0.001). A cutoff ADC value of 0.98×10⁻³ mm²/s was used to distinguish between benign and malignant lesions, yielding 85.3% sensitivity and 78.6% specificity. The median ADC value of lymphomas (0.44×10⁻³ mm²/s; range, 0.39–0.58×10⁻³ mm²/s) was significantly smaller (P < 0.001) than that of squamous cell carcinomas (median ADC value 0.72×10⁻³ mm²/s; range, 0.65–1.06×10⁻³ mm²/s). There was no significant difference between median ADC values of inflammatory (1.13×10⁻³ mm²/s; range, 0.85–2.38×10⁻³ mm²/s) and noninflammatory benign lesions (1.26×10⁻³ mm²/s; range, 0.52–2.33×10⁻³ mm²/s).

CONCLUSION

Diffusion-weighted imaging and the ADC values can be used to differentiate and characterize benign and malignant head and neck lesions.Diagnosis of head and neck lesions is difficult due to the complicated anatomic structure and different histological components of the many tissues that the neck contains. Imaging of head and neck lesions is not only important for diagnosis of lesions, but also for differentiation of benign lesions from malignant lesions and staging of tumors. While conventional imaging methods mainly evaluate morphological properties, their value is limited in recognizing prognostic characteristics such as benign-malignant differentiation of lesions (1). Routine magnetic resonance imaging (MRI) is a time-consuming method, which is sensitive to differences between examiners and may require the use of contrast material. With development of rapid MRI sequences (such as echo-planar [EPI], fast advanced spin echo [FASE], split echo acquisition of fast spin echo [SPLICE]), the sensitivity to susceptibility artifacts limiting the use of MRI for the head and neck region and limitations linked to duration have been significantly reduced (2, 3).Diffusion-weighted magnetic resonance imaging (DW-MRI) is a short sequence produced from EPI, FASE, SPLICE sequences. DW-MRI is sensitive to the randomized (Brownian) motion of water molecules at a microscopic level, which provides functional information about tissues. DW-MRI was initially used to diagnose early stroke in the brain and to evaluate brain masses (4–6). Previous studies have shown that rapid growth of high-grade tumors like astrocytoma and lymphoma causes hypercellularity, which leads to limitation of the diffusion of water molecules. Nowadays, apparent diffusion coefficient (ADC) maps calculated from DW-MRI sequences are being increasingly used to provide quantitative data for head and neck lesion diagnosis. In malignant lesions, the DW-MRI signal increases and signal loss is observed on ADC maps (5, 7, 8). Many researchers benefited from this feature of DW-MRI and evaluated the effectiveness of DW-MRI for head and neck lesion identification, benign-malignant differentiation, and characterization of malignant lesions (9–11).In this prospective study, head and neck lesions that are seen in daily routine were evaluated using DW-MRI, and the role of ADC values in lesion characterization was investigated with the guidance of histopathological results.     

Effect on therapeutic ratio of planning a boosted radiotherapy dose to the dominant intraprostatic tumour lesion within the prostate based on multifunctional MR parameters

Objective:

To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose.

Methods:

The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T₂ maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose–volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan.

Results:

Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1 ± 0.6 vs 72.7 ± 0.3 Gy; p < 0.001) and decreased for the rectum (38.2 ± 2.5 vs 43.5 ± 2.5 Gy; p < 0.001) and the bladder (29.1 ± 9.0 vs 36.9 ± 9.3 Gy; p < 0.001) for the boosted plan. The prostate TCP was increased (80.1 ± 1.3 vs 75.3 ± 0.9 Gy; p < 0.001) and rectal NTCP lowered (3.84 ± 3.65 vs 9.70 ± 5.68 Gy; p = 0.04) in the boosted plan. The bladder NTCP was negligible for both plans.

Conclusion:

Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found.

Advances in knowledge:

The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio.Phase III trials using conformal external beam radiotherapy have shown that a dose escalation improves biochemical progression-free survival in patients with prostate cancer;^1–5 however, increases in late rectal and urinary morbidity are associated with the dose distributions used to achieve these gains.With the advent of intensity-modulated radiotherapy (IMRT), complex three-dimensional (3D) dose distributions can be delivered to areas of disease whilst reducing the dose to the surrounding tissues and also potentially boosting the dose to encompassed small volumes such as the dominant intraprostatic lesions (DILs). This is potentially advantageous, as local recurrence has been shown to originate within the initial tumour volume.⁶This approach requires reliable and reproducible imaging to identify the DIL. Conventional MR using high spatial resolution T₂ weighted (T2W) contrast has insufficient sensitivity and specificity for defining the tumour within the prostate gland, especially if the lesions are <1 cm in diameter.⁷ A combination of MRI methods whose contrast is determined by tissue physiology and biochemistry rather than anatomy offers improved sensitivity and specificity for delineation of prostate cancers. Functional methods include diffusion-weighted imaging, MR spectroscopic imaging (MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) and together present a multiparametric MRI (mpMRI) data set. We have previously validated a multiparametric model to identify prostate cancer and the location of DILs with histology from prostatectomy specimens.⁸mpMRI data are reliable only if acquired before androgen deprivation (hormone) therapy, as there is profound functional signal degradation after hormone therapy.^9–11 Our standard institutional practice for intermediate- and high-risk localized prostate cancer uses hormone therapy for 3–6 months prior to external beam radiotherapy,^12–14 so modelling a radiation boost to mpMRI-defined tumour nodules requires acquisition of functional data before hormone therapy to be registered with anatomical images obtained post hormone treatment and immediately prior to radiotherapy¹⁵ in order to translate the tumour location to radiotherapy planning CT images. The aim of this planning study therefore was to demonstrate the use of a mpMRI-defined DIL to create a radiotherapy boost volume. IMRT treatment plans were optimized to deliver either a uniform 74 Gy to the whole prostate or to add an 8-Gy simultaneous integrated boost to the DIL, and the potential clinical outcomes compared using dose–volume histograms (DVHs) and radiobiological models for tumour control probability (TCP) and normal tissue complication probabilities (NTCPs).     

Variation in patient position and impact on carbon-ion scanning beam distribution during prostate treatment

Objective:

We assessed the impact of changes in patient position on carbon-ion scanning beam distribution during treatment for prostate cancer.

Methods:

68 patients were selected. Carbon-ion scanning dose was calculated. Two different planning target volumes (PTVs) were defined: PTV1 was the clinical target volume plus a set-up margin for the anterior/lateral sides and posterior side, while PTV2 was the same as PTV1 minus the posterior side. Total prescribed doses of 34.4 Gy [relative biological effectiveness (RBE)] and 17.2 Gy (RBE) were given to PTV1 and PTV2, respectively. To estimate the influence of geometric variations on dose distribution, the dose was recalculated on the rigidly shifted single planning CT based on two dimensional–three dimensional rigid registration of the orthogonal radiographs before and after treatment for the fraction of maximum positional changes.

Results:

Intrafractional patient positional change values averaged over all patients throughout the treatment course were less than the target registration error = 2.00 mm and angular error = 1.27°. However, these maximum positional errors did not occur in all 12 treatment fractions. Even though large positional changes occurred during irradiation in all treatment fractions, lowest dose encompassing 95% of the target (D₉₅)-PTV1 was >98% of the prescribed dose.

Conclusion:

Intrafractional patient positional changes occurred during treatment beam irradiation and degraded carbon-ion beam dose distribution. Our evaluation did not consider non-rigid deformations, however, dose distribution was still within clinically acceptable levels.

Advances in knowledge:

Inter- and intrafractional changes did not affect carbon-ion beam prostate treatment accuracy.The depth dose distribution for a charged particle beam exhibits a Bragg peak at the end of range, which is particularly sensitive to variation in tissue density along its path length. For this reason, changes in patient position perturb charged particle beams more strongly than photon beams.¹ Of the two major treatment uncertainties, intrafractional motion and interfractional changes, treatment accuracy for the prostate appears more strongly affected by interfractional changes.^2–7 Clinical protocols now incorporate several approaches to overcoming these uncertainties, including acquisition of radiographs or cone beam CT images.However, despite these technical solutions to intra- and interfractional changes and improvements in patient positional accuracy during the patient set-up procedure, treatment accuracy may also be affected by positional changes during treatment. Most treatment centres do not check patient positional accuracy after treatment beam irradiation, because approaches to adjusting distribution in the next fraction to compensate for under-/overdosage in the preceding have not been developed and because patient position is assumed not to change during treatment. Our hospital has been providing carbon-ion scanning beam treatment since 2011.⁸ The average time from complete patient set-up to complete beam irradiation was 2.6 min. Although this is relatively short, we have no quantitative data on the effect of patient positional change on carbon-ion scanning dose distribution.In this study, we evaluated patient positional change during treatment and its impact on carbon-ion scanning dose distribution in treatment of the prostate.     

Assessment of the robustness of volumetric-modulated arc therapy for lung radiotherapy

Volumetric-modulated arc therapy (VMAT) is increasingly popular as a treatment method in radiotherapy owing to the speed with which treatments can be delivered. However, there has been little investigation into the effect of increased modulation in lung plans with regard to interfraction organ motion. This is most likely to occur where the planning target volume (PTV) lies within areas of low density. This paper aims to investigate the effect of modulation on the dose distribution using simulated patient movement and to propose a method that is less susceptible to such movement. Simulated interfraction motion is achieved by moving the plan isocentre in steps of 0.5 cm and 1.0 cm in six directions for five clinical VMAT patients. The proposed planning method involves optimisation using a density override of 1 g cm⁻³, within the PTV in lung, to reduce segment boosting in the periphery of the PTV. This investigation shows that modulation can result in an increase in the maximum dose of >25%, an increase in PTV near-maximum dose of 17% and a reduction in near-minimum dose by 46%. Unacceptable organ at risk (OAR) doses are also seen. The proposed method reduces modulation, resulting in a maximum dose increase of 10%. Although safeguards are in place to prevent the increased dose to OARs from patient movement, there is nothing to prevent the increased dose as a result of modulation in lung. A simple planning method is proposed to safeguard against this effect. Investigation suggests that, where modulation exists in a plan, this method reduces it and is clinically viable.Volumetric-modulated arc therapy (VMAT) is becoming increasingly popular as a treatment method in radiotherapy owing to the speed with which treatments can be delivered [1, 2] and the benefit to dose distribution. This benefit is clear in patients with concave planning target volumes (PTVs) near organs at risk (OARs) [1, 3]. Several studies have compared VMAT with intensity-modulated radiotherapy and conventional plans for lung cancer with a favourable outcome [4–7]. Although there have been recent investigations into the effect of breathing motion [8] and the interplay effect, there has been little investigation into the effect of interfraction internal patient movement [9, 10] on the dose distribution.Where part of the PTV comprises air or low-density tissue (i.e. lung), the optimiser attempts to boost the dose to these regions to attain coverage with the 95% isodose line despite the lack of tissue providing scatter. This can result in highly modulated plans. This “boosting” effect occurs owing to a lack of the scatter material present in the beam and results in horns in the fluence profile. The effect also occurs in situations where any PTV is positioned near the patient’s skin [11,p. 56–58].The boosting effect is undesirable for two reasons. Firstly, it is unnecessary to produce the same dose to the PTV in air as the PTV in tumour tissue. As long as the PTV in air is being exposed to the same fluence as the PTV in tissue, then the tumour grows or moves into a region of air, the higher dose will follow it. However, if the plan is modulated to boost the dose to the PTV in air, then organ movement causes a deviation from the planning CT geometry, very high doses can be seen in regions where tissue falls within a boosted part of the beam. This may occur in lung patients as the tumour regresses or owing to atelectasis. In situations where daily imaging and breath-hold devices or gating are not used, consideration should be given as to whether it is appropriate to deliver modulated VMAT plans for lung patients.There are three options for avoiding unwanted modulation in air in an optimised VMAT plan. Firstly, an edited PTV can be used for optimising, which does not extend fully into the lung, thus preventing the need for any dose boosting in the lung. Alternatively, a bolus on the skin surface can be used to provide scatter in order to increase the dose to the skin region without boosting. However, this is not applicable in the lung. A third alternative is to optimise using a fake bolus, providing the scatter material to prevent boosting, and then to remove the bolus for the final dose calculation of the clinical plan. This results in poorer peripheral coverage near the skin surface or in the lung, compared with using a real bolus, but allows for patient movement within the fake bolus region without any dose boosting. In conformal plans, this could be achieved by pulling back multileaf collimators (MLCs) or jaws.This paper aims to investigate the effect of patient movement on the dose distribution for the clinical plan of five patients treated with a single VMAT arc. An alternative method of planning is proposed using a density override of the PTV in lung to 1 g cm⁻³ (i.e. a fake bolus) to reduce the boosting effect. This method is investigated to determine whether it increases the safety of modulated arc therapy in the case of internal organ movement and uncertainties in patient set-up.     

Quantification of Pancreas Surface Lobularity on CT: A Feasibility Study in the Normal Pancreas

ObjectiveTo assess the feasibility and reproducibility of pancreatic surface lobularity (PSL) quantification derived from abdominal computed tomography (CT) in a population of patients free from pancreatic disease.Materials and MethodsThis retrospective study included 265 patients free from pancreatic disease who underwent contrast-enhanced abdominal CT between 2017 and 2019. A maximum of 11 individual PSL measurements were performed by two abdominal radiologists (head [5 measurements], body, and tail [3 measurements each]) using dedicated software. The influence of age, body mass index (BMI), and sex on PSL was assessed using the Pearson correlation and repeated measurements. Inter-reader agreement was assessed using the intraclass correlation coefficient (ICC) and Bland Altman (BA) plots.ResultsCT images of 15 (6%) patients could not be analyzed. A total of 2750 measurements were performed in the remaining 250 patients (143 male [57%], mean age 45 years [range, 18–91]), and 2237 (81%) values were obtained in the head 951/1250 (76%), body 609/750 (81%), and tail 677/750 (90%). The mean ± standard deviation PSL was 6.53 ± 1.37. The mean PSL was significantly higher in male than in female (6.89 ± 1.30 vs. 6.06 ± 1.31, respectively, p < 0.001). PSL gradually increased with age (r = 0.32, p < 0.001) and BMI (r = 0.32, p < 0.001). Inter-reader agreement was excellent (ICC 0.82 [95% confidence interval 0.72–0.85], with a BA bias of 0.30 and 95% limits of agreement of −1.29 and 1.89).ConclusionCT-based PSL quantification is feasible with a high success rate and inter-reader agreement in subjects free from pancreatic disease. Significant variations were observed according to sex, age, and BMI. This study provides a reference for future studies.     

Pilot study on interfractional and intrafractional movements using surface infrared markers and EPID for patients with rectal cancer treated in the prone position

Objective:

To evaluate interfractional and intrafractional movement of patients with rectal cancer during radiotherapy with electronic portal imaging device (EPID) and surface infrared (IR) markers.

Methods:

20 patients undergoing radiotherapy for rectal cancer with body mass index ranging from 18.5 to 30 were enrolled. Patients were placed in the prone position on a couch with a leg pillow. Three IR markers were put on the surface of each patient and traced by two stereo cameras during radiotherapy on a twice-weekly basis. Interfractional isocentre movement was obtained with EPID images on a weekly basis. Movement of the IR markers was analysed in correlation with the isocentre movement obtained from the EPID images.

Results:

The maximum right-to-left (R-L) movement of the laterally located markers in the horizontal isocentre plane was correlated with isocentre translocation with statistical significance (p = 0.018 and 0.015, respectively). Movement of the surface markers was cyclical. For centrally located markers, the 95% confidence intervals for the average amplitude in the R-L, cranial-to-caudal (C-C) and anterior-to-posterior (A-P) directions were 0.86, 2.25 and 3.48 mm, respectively. In 10 patients, intrafractional movement exceeding 5 mm in at least one direction was observed. Time-dependent systematic movement of surface markers during treatment, which consisted of continuous movement towards the cranial direction and a sail back motion in the A-P direction, was also observed.

Conclusion:

Intrafractional movement of surface markers has both cyclic components and time-dependent systematic components. Marker deviations exceeding 5 mm were mainly seen in the A-P direction. Pre- or post-treatment EPID images may not provide adequate information regarding intrafractional movement because of systematic movement in the A-P direction during radiotherapy.

Advances in knowledge:

This work uncovered a sail back motion of patients in the A-P direction during radiotherapy. Pre- or post-treatment EPID images may not provide accurate positioning of patients in the A-P direction because of this time-dependent intrafractional motion.Patients treated in the prone position are reported to be more susceptible to positioning errors during radiotherapy.^1–3 Set-up errors in relation to patient position have been frequently reported in patients treated for prostate cancer. Bayley et al¹ showed that for patients with prostate cancer treated in the prone position, isocentre positioning errors were 0.0 ± 3.7 and 0.1 ± 4.3 mm in the anterior-to-posterior (A-P) and cranial-to-caudal (C-C) directions, respectively. Isocentre positioning errors ranged from −7.6 to 8.8 mm in the A-P direction. However, for errors in the C-C direction, there was no significant difference between the supine and prone positions. Weber et al² also reported that the prone position was more unstable than the supine position with a greater distribution of isocentre translocation (prone 4.7 mm vs supine 4.2 mm) in the A-P direction. In addition, systematic set-up variation was larger in the prone position than in the supine position (2.7 vs 1.9 mm). Griffiths et al³ demonstrated that the probability of set-up errors exceeding 5 mm was 12% in the right-to-left (R-L) direction and 33% in the C-C direction. These findings suggest that efforts should be made to reduce set-up uncertainties for patients, especially those treated in the prone position, for more accurate treatment delivery, specifically in an era of intensity-modulated radiotherapy and image-guided radiotherapy. Unlike prostate cancer, patients with rectal cancer are advised to be treated in the prone position to minimize the radiation exposure to the small bowel. But set-up instabilities for patients with rectal cancer have not been studied as much as those for patients with prostate cancer, as described above.As one of the methods of monitoring patient motion, a non-invasive infrared (IR) monitoring system within the radiotherapy treatment room has been established at the Department of Radiation Oncology, Seoul National University Hospital, Seoul, Republic of Korea, and the reliability of the system has previously been reported.⁴ An IR monitoring system as a tool for measuring patient motion can be easily set up using IR cameras and IR markers that are placed on the surface of the patient. This system is not only non-invasive but is also capable of detecting surface motion in real time.The primary goals of this pilot study were to monitor and analyse patterns in patient motion, which may consist of systematic and/or random components, during radiotherapy using the IR monitoring system. The secondary goal was to validate the applicability of the IR monitoring system by correlation with electronic portal imaging device (EPID) images.     

Grading of small hepatocellular carcinomas (≤2 cm): correlation between histology,T2 and diffusion-weighted imaging

Objective:

To evaluate the capacity of diffusion-weighted imaging (DWI) to determine the histological grade of small-sized hepatocellular carcinomas (HCCs) in liver cirrhosis in comparison with T₂ weighted imaging.

Methods:

51 cirrhotic patients with 63 histologically proven HCCs ≤2 cm underwent abdominal MRI, including DWI (b-values 50, 400 and 800 s mm⁻²) and T₂ weighted sequences. HCCs were classified into well-differentiated HCCs (n = 37) and moderately differentiated HCCs (n = 26). Relative contrast ratios (RCRs) between the lesions and the surrounding liver were performed and compared between the two groups for T₂ weighted images, each b-value and apparent diffusion coefficients (ADCs). A receiver operating characteristic (ROC) analysis was performed to compare RCRs in T₂ and diffusion-weighted images.

Results:

We found significant differences in RCRs between well-differentiated vs moderately differentiated HCCs for b = 50, 400 and 800 s mm⁻² and T₂ weighted images (1.35 ± 0.36 vs 1.86 ± 0.62; 1.35 ± 0.38 vs 1.82 ± 0.60; 1.27 ± 0.30 vs 1.74 ± 0.53; 1.14 ± 0.18 vs 1.43 ± 0.28, respectively; p < 0.001), whereas no significant differences were observed in ADC and ADC RCR (1.05 ± 0.19 vs 0.99 ± 0.15 and 1.1 ± 0.22 vs 1.09 ± 0.23; p = 0.16 and p = 0.82, respectively). No significant difference was found in the areas under the ROC curve for RCRs of T₂ weighted images and every DWI b-value (p = 0.18).

Conclusion:

The RCR measurement performed in DWI 50, 400 and 800 b-values and T₂ demonstrated a significant difference between well-differentiated and moderately differentiated small-sized HCCs. Furthermore, no difference was shown by using either ADC or ADC RCR.

Advances in knowledge:

DWI with RCR measurement may be a valuable tool for non-invasively predicting the histological grade of small HCCs.Recent advances in liver imaging techniques and a better understanding of imaging findings have facilitated the detection of small nodules in cirrhotic livers. Nodular lesions ≤2 cm against a background of cirrhosis are diagnostically challenging in daily practice.¹ The early and accurate diagnosis of hepatocellular carcinomas (HCCs) is of great importance because the best treatment results are obtained in patients with small and non-invasive HCCs.^2,3 If small HCCs are not treated, they can grow aggressively and microscopic vascular invasion can occur before the 2-cm cut-off size for small HCCs.¹ Fukuda et al⁴ reported that moderately and poorly differentiated HCCs ≤2 cm have a greater tendency towards microvascular invasion, meaning that the malignant potential of small HCCs should also be taken into account when selecting a treatment. Therefore, the accurate distinction of well-differentiated HCCs from less well-differentiated HCCs is also considered an important issue in planning of the therapeutic strategy, even if the tumour is small.^5,6 Considering that histological confirmation of small suspicious hepatic nodules before treatment is often not possible owing to their location in the liver or the risks of track seeding, the role of a non-invasive pre-operative imaging technique for the discrimination of moderate to poorly differentiated HCCs from well-differentiated HCCs is important. Diffusion-weighted imaging (DWI) allows the characterization of microscopic proton displacement and has profoundly improved oncological imaging. Owing to the recent advances in MRI technology, DWI can be applied to liver imaging with improved image quality.⁷ Several clinical trials have demonstrated the benefit of DWI in the detection and characterization of focal liver lesions.^8–11 There have been attempts to correlate DWI findings with the histological grading of HCCs using signal intensity (SI) and apparent diffusion coefficient (ADC) values, but no consensus in the results was obtained.^12–18 To the best of our knowledge, the interplay between DWI and histopathological factors in a cohort of patients with exclusively small HCCs (<2 cm) has not been specifically investigated. The purpose of the present study was to investigate whether or not diffusion-weighted (DW) images and ADC could determine the histological grading of HCCs <2 cm in diameter.     

4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT

Objective:

To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability () using an in-house developed dose model.

Methods:

Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain for each plan.

Results:

The average variation observed in mean dose to the target volumes were −0.76% ± 0.36% for the 20-fraction treatment and −0.26% ± 0.68% and −1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in was −1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was −2.80% ± 1.68% and −4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min⁻¹ for the single-fraction treatments, the drop in was reduced by approximately 1.5%.

Conclusion:

The effect of interplay on is negligible for conventionally fractionated treatments, whereas considerable drop in is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect.

Advances in knowledge:

A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on .Respiration-induced organ motion represents a serious challenge regarding the accuracy of dose delivery in radiotherapy (RT) and its impact on clinical outcome. Lung tumours are the most common tumours affected by respiration-induced motion, and local failure (approximately 70% of the cases) is considered as a major cause of tumour-related deaths. Studies have highlighted the importance of dose escalation for improving local control in non-small-cell lung cancers (NSCLC).^1,2Since intensity-modulated RT (IMRT) has the potential to deliver higher doses with fewer normal tissue complications,³ IMRT is often used nowadays to treat lung tumours. Moreover, hypofractionated treatments have been shown to result in better clinical outcomes for medically inoperable early-stage lung tumours.^4–7 Better targeting accuracy coupled with superior normal tissue sparing and higher dose conformality, especially with smaller treatment fields used in stereotactic treatments, allows clinicians to prescribe extremely high doses in very few fractions (approximately three). With the advent of image-guided RT, this type of treatment is becoming increasingly common for lung RT. In conventional treatments where the fluence is uniform at the central portion of the fields, respiration-induced tumour motion causes dose blurring at the edges of the target volume, which can be accounted for by a sufficient planning target volume (PTV) margin. However, in multileaf collimator (MLC)-based IMRT delivery where the fluence is non-uniform across the fields, the interplay between respiration-induced tumour motion and the movement of MLC leaves can result in undesired motion artefacts in dose delivery.^8,9 Consequently, motion management or correction techniques such as tumour tracking or gating have been suggested for treating moving tumours with IMRT.^10–13 It should also be noted that lung tumours have one of the steepest dose–response curves (γ₅₀ = 3.9),¹⁴ which means that a small change in dose results in a relatively large change in tumour control probability (TCP). Although motion management techniques are currently available, it may not be possible to use such techniques for each patient either owing to time or resource constraints. Thus, it is important to understand and quantify the effect of tumour motion in IMRT treatments, that is, the interplay effect, in the absence of tumour tracking or gating. By quantifying, we mean not only in terms of absorbed dose, a purely physical quantity, but more importantly in terms of changes in the probability of local tumour control.Several studies have investigated the effect of respiration-induced tumour motion on IMRT treatments.^9,15–20 Jiang et al¹⁵ have investigated the effect of interplay for three different modes of IMRT delivery (step-and-shoot with 10 and 20 intensity levels, sliding window) using a 0.6-cm³ farmer chamber positioned at the centre of the artificial tumour in a moving phantom. They found that the mean dose to the moving tumour for all the fields varies from <2% to 3%, but it could be as high as 30% for a single field. They have also shown that the variation in dose is insensitive to the mode of delivery and the dose differences due to interplay decrease as the number of treatment fractions becomes large (approximately 30). This has been previously emphasized by Bortfeld et al⁹ who showed by statistical analysis that the mean dose to a moving tumour is insensitive to the delivery technique, and the standard deviation (SD) in dose for a 30-fraction treatment is generally <1% of the mean dose. However, the conclusion derived from point-dose measurements by Jiang et al does not provide a complete picture of the interplay effect to the overall tumour volume. Using two-dimensional (2D) film measurements, Berbeco et al²¹ have shown that the SD of the dose to a pixel inside the target volume can be as high as 2–4% for single-fraction treatments, which corresponds to stereotactic radiosurgery, although the effect is reduced to 0.4–0.7% with 30 fractions. According to their measurements, the maximum dose in the target varies <1%, while the minimum dose varies up to approximately 6%. This indicates that there could be considerable underdosage of the target volume even for treatments with large number of fractions and the effect of interplay is significant for hypofractionated treatments. In a recent study by Zhao et al²² in a three-fraction treatment, the results showed that the clinical target volume (CTV) could be considerably underdosed owing to the interplay effect in a Cyberknife® treatment (Accuray Inc., Sunnyvale, CA). Furthermore, Seco et al²³ have emphasized that reduced dose errors owing to the interplay effect in many-fraction treatments will not apply to hypofractionated treatments. Nevertheless, the effect of tumour motion and MLC leaves remains a concern for hypofractionated treatments, and this has been emphasized by American Association of Physicists in Medicine report 91.²⁴Although there are numerous studies addressing the issues of interplay effects in terms of dose variation in the tumour, studies quantifying the clinical significance of these dose variations are much rarer. Use of TCP as a metric would provide a more valuable insight into the true significance of the interplay effect. As mentioned by Niemierko,²⁵ it would be interesting to know the clinical significance of “x” amount of dose error and “y” amount of geometric error rather than mere variation in the dose. Duan et al¹⁸ have performed a TCP analysis using a moving phantom and found the TCP changes to be 2.3% and 4.3% for five- and single-fraction treatments. However, the volume of the target used in their study is fixed (4.5-cm diameter sphere). TCP values could significantly differ with the volume of the target even for the same prescribed dose with a uniform clonogen density in the CTV, which is the case in this study. Moreover, the TCP values provided were not calculated from a large number of simulations, which raises concern over its applicability for a population of patients.     

T1 Recovery Is Predominantly Found in Black Holes and Is Associated with Clinical Improvement in Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE:Quantitative MR imaging parameters help to evaluate disease progression in multiple sclerosis and increase correlation with clinical disability. We therefore hypothesized that T1 values might be a marker for ongoing tissue damage or even remyelination and may help increase clinical correlation.MATERIALS AND METHODS:MR imaging was performed in 17 patients with relapsing-remitting MS at baseline and after 12 months of starting immunotherapy with dimethyl fumarate. On baseline images, lesion segmentation was performed for normal-appearing white matter, T2 hyperintense (FLAIR lesions), T1 hypointense (black holes), and contrast-enhancing lesions, and T1 relaxation times were obtained at baseline and after 12 months. Changes in clinical status were assessed by using the Expanded Disability Status Scale and Symbol Digit Modalities Test at both dates (Expanded Disability Status Scale-difference/Symbol Digit Modalities Test-diff).RESULTS:The highest T1 relaxation time at baseline was measured in black holes (1460.2 ± 209.46 ms) followed by FLAIR lesions (1400.38 ± 189.1 ms), pure FLAIR lesions (1327.5 ± 210.04 ms), contrast-enhancing lesions (1205.59 ± 199.95 ms), and normal-appearing white matter (851.34 ± 30.61 ms). After 12 months, T1 values had decreased significantly in black holes (1369.4 ± 267.81 ms), contrast-enhancing lesions (1079.57 ± 183.36 ms) (both P < .001), and normal-appearing white matter (841.98 ± 36.1 ms, P = .006). With the Jonckheere-Terpstra Test, better clinical scores were associated with decreasing T1 relaxation times in black holes (P < .05).CONCLUSIONS:T1 relaxation time is a useful quantitative MR imaging technique, which helps detect changes in MS lesions with time. We assume that these changes are associated with the degree of myelination within the lesions themselves and are pronounced in black holes. Additionally, decreasing T1 values in black holes were associated with clinical improvement.

MR imaging is an established tool in diagnosing multiple sclerosis and in monitoring inflammatory disease progression. In clinical routine, T2 and T1 lesion load and the detection of contrast-enhancing lesions (CE-Ls) are commonly used for monitoring subclinical disease activity and evaluating the effectiveness of pharmaceutical treatments. While hyperintense lesions on T2-weighted images (FLAIR lesions) correspond to a wide spectrum of histopathologic changes, ranging from edema and mild demyelination to glial scars or liquid necrosis, nonenhancing T1 hypointense lesions, black holes (BHs), are reported to be more specific markers for demyelination, axonal loss, and tissue damage.^1–6 It was observed that for discriminating the different stages of cell damage, the degree of BH hypointensity seems to reflect the extent of axonal loss and might distinguish demyelinated and partially remyelinated lesions.^7,8 Consequently, T1 relaxation times (T1-RTs) are increased in edema, demyelination, and axonal loss.^9–11A recent study showed that the assessment of MS lesions by their T1 values helps to increase correlations with disability and might lead to a more differentiated lesion classification.¹² However, little is known about the potential of lesional T1 values as a clinical marker in disease progression. Only a small number of previous studies have applied T1 relaxometry in patients with MS and reported increased T1 values in normal-appearing white matter (NAWM).^13,14 Therefore, our study focuses on the longitudinal evaluation of T1 values in different MS lesion types, representing different grades of tissue destruction. With the recently introduced double inversion-contrast magnetization-prepared rapid acquisition of gradient echo (MP2RAGE) sequences, it is now possible to generate quantitative T1 maps with high reproducibility.¹⁵The purpose of this study was to observe the evolution of T1 values in NAWM and in lesions in patients with MS for 1 year after starting immunotherapy with dimethyl fumarate. We hypothesized that longitudinal changes of lesional T1 values are associated with changes in clinical disability because T1 values might be a marker for ongoing tissue damage or even remyelination.     

Spatial variation in T1 of healthy human articular cartilage of the knee joint

The longitudiual relaxation time T₁ of native cartilage is frequently assumed to be constant. To redress this, the spatial variation of T₁ in unenhanced healthy human knee cartilage in different compartments and cartilage layers was investigated. Knees of 25 volunteers were examined on a 1.5 T MRI system. A three-dimensional gradient-echo sequence with a variable flip angle, in combination with parallel imaging, was used for rapid T₁ mapping of the whole knee. Regions of interest (ROIs) were defined in five different cartilage segments (medial and lateral femoral cartilage, medial and lateral tibial cartilage and patellar cartilage). Pooled histograms and averaged profiles across the cartilage thickness were generated. The mean values were compared for global variance using the Kruskal–Wallis test and pairwise using the Mann–Whitney U-test. Mean T₁ decreased from 900–1100 ms in superficial cartilage to 400–500 ms in deep cartilage. The averaged T₁ value of the medial femoral cartilage was 702±68 ms, of the lateral femoral cartilage 630±75 ms, of the medial tibial cartilage 700±87 ms, of the lateral tibial cartilage 594±74 ms and of the patellar cartilage 666±78 ms. There were significant differences between the medial and lateral compartment (p<0.01). In each cartilage segment, T₁ decreased considerably from superficial to deep cartilage. Only small variations of T₁ between different cartilage segments were found but with a significant difference between the medial and lateral compartments.MRI relaxation parameters are used to evaluate cartilage degradation. T₂ has been investigated extensively and has been demonstrated to vary with water and collagen content and with collagen orientation in the different cartilage layers [1–8].The quantification of the longitudiual relaxation time T₁ of native cartilage has received less attention. In experimental studies, native T₁ has been demonstrated to correlate with mechanical properties [9] and to depend upon the macromolecular structure of cartilage [10]. However, it is frequently assumed to be constant across cartilage [11–13]. A few studies have investigated the mean values of a single compartment (10, 14–19] but have not investigated the depth-dependent variation. To our knowledge, no study has systematically compared T₁ of unenhanced human knee cartilage in different cartilage layers and in different cartilage compartments in healthy volunteers.

Table 1

T₁ of healthy human articular cartilage in the knee joint

Imaging of early pancreatic cancer on multidetector row helical computed tomography

Early pancreatic cancer is small and limited to the pancreas. In contrast, small pancreatic cancer may include peripancreatic vasculature or metastasis involvement. This study evaluates images of early pancreatic cancer on multidetector CT (MDCT) using contrast-enhanced multiphasic imaging, and post-processed pancreatic duct images. CT findings and pathological features were analysed in eight patients with early pancreatic cancer. Pathological evaluation included location, size and histological grading of the tumour. MDCT evaluation covered the maximum diameter of the main pancreatic duct (MPD), stenosis or obstruction of the MPD, loss of normal lobar texture and associated pancreatitis. Attenuation differences between normal pancreatic parenchyma and the tumour (AD–PT) were also measured. Focal stenosis or obstruction of the MPD with dilatation of the distal MPD was demonstrated in all patients. Associated pancreatitis occurred in six patients with tumours measuring 12 mm or greater. Loss of normal lobar texture was recognised in four cases with the tumour measuring 14 mm or greater. Statistically, low-attenuated lesions and high-attenuated lesions differed with respect to the tumour size (p<0.01), and a positive relationship was demonstrated between the tumour size and AD–PT (r = 0.84). In seven cases, AD–PT is higher during the arterial phase than the pancreatic phase. Early pancreatic cancer appears as low attenuation on early phase, and as high- to iso-attenuation during the pancreatic and delayed phases in respect to the tumour size. Focal stenosis or obstruction of the MPD with dilatation of the distal MPD observed on curved reformation imaging seems important in the diagnosis of early pancreatic cancer.It is well known that pancreatic cancer is rarely cured and often fatal. Surgical resection is currently the only potentially curative treatment for pancreatic carcinoma, and detection of pancreatic cancer at an early stage is very important for increasing the resectability of the tumour and improving prognosis. Stage I pancreatic cancer, or early pancreatic cancer, is defined as a tumour smaller than 2 cm by histological measurement, limited to the pancreas without invasion to the peripancreatic vasculature, lymph node metastasis or distant metastasis [1]. It is generally known that the smaller the tumour size and the earlier the clinical stage, the better the prognosis. Small pancreatic cancer is defined as a tumour smaller than 2 cm with or without invasion to the peripancreatic vasculature or metastasis.Contrast-enhanced helical CT has facilitated the detection and staging of pancreatic cancer and is accepted as one of the most effective imaging techniques for the diagnosis of pancreatic cancer [2–10]. Current multidetector row helical CT (MDCT) can provide imaging details of pancreatic lesions, and some studies have reported on the imaging of small pancreatic cancer [4], but limited data are available comparing small and early pancreatic cancer.In the present retrospective study, we evaluated images of small and early pancreatic cancer on MDCT using contrast-enhanced multiphasic imaging and post-processed pancreatic duct images and compared them with the pathological findings of surgical specimens.     

Photon counting spectral CT component analysis of coronary artery atherosclerotic plaque samples

Objective:

To evaluate the capabilities of photon counting spectral CT to differentiate components of coronary atherosclerotic plaque based on differences in spectral attenuation and iodine-based contrast agent concentration.

Methods:

10 calcified and 13 lipid-rich non-calcified histologically demonstrated atheromatous plaques from post-mortem human coronary arteries were scanned with a photon counting spectral CT scanner. Individual photons were counted and classified in one of six energy bins from 25 to 70 keV. Based on a maximum likelihood approach, maps of photoelectric absorption (PA), Compton scattering (CS) and iodine concentration (IC) were reconstructed. Intensity measurements were performed on each map in the vessel wall, the surrounding perivascular fat and the lipid-rich and the calcified plaques. PA and CS values are expressed relative to pure water values. A comparison between these different elements was performed using Kruskal–Wallis tests with pairwise post hoc Mann–Whitney U-tests and Sidak p-value adjustments.

Results:

Results for vessel wall, surrounding perivascular fat and lipid-rich and calcified plaques were, respectively, 1.19 ± 0.09, 0.73 ± 0.05, 1.08 ± 0.14 and 17.79 ± 6.70 for PA; 0.96 ± 0.02, 0.83 ± 0.02, 0.91 ± 0.03 and 2.53 ± 0.63 for CS; and 83.3 ± 10.1, 37.6 ± 8.1, 55.2 ± 14.0 and 4.9 ± 20.0 mmol l⁻¹ for IC, with a significant difference between all tissues for PA, CS and IC (p < 0.012).

Conclusion:

This study demonstrates the capability of energy-sensitive photon counting spectral CT to differentiate between calcifications and iodine-infused regions of human coronary artery atherosclerotic plaque samples by analysing differences in spectral attenuation and iodine-based contrast agent concentration.

Advances in knowledge:

Photon counting spectral CT is a promising technique to identify plaque components by analysing differences in iodine-based contrast agent concentration, photoelectric attenuation and Compton scattering.The role of atherosclerotic plaque rupture in acute coronary events is well established.¹ Plaques prone to rupture display a large lipid-rich core, a thin fibrous cap and an inflammatory infiltration.² CT is now considered as a reliable tool to assess coronary artery stenosis,³ but still has two main shortcomings. Firstly, differentiating between intraluminal iodine-based contrast agent and plaque calcification remains challenging in small vessels such as the coronary arteries, leading to an erroneous estimation of the degree of stenosis. Secondly, CT is limited in correctly identifying plaque components, especially for the detection of the lipid core out of the normal wall or the fibrous plaque components.^4–8 These problems are related to the insufficient spatial resolution available with the current clinical system and to the overlaps of the Hounsfield values between iodine and calcifications on one hand and the lipid core and other soft components of the arterial wall on the other hand. Improved differentiation between calcification and iodine was obtained with energy CT.^8,9Furthermore, photon counting spectral CT has recently been proposed to improve tissue characterization by improving the measurement of the energy dependence of the attenuation of various tissues in comparison with conventional CT scanners. This spectral resolution allows obtaining a map of the iodine concentration (IC) by utilizing its K-edge at 33.2 keV in the X-ray absorption spectrum, as well as an accurate decomposition of the X-ray attenuation into photoelectric absorption (PA) and Compton scattering (CS) instead of a single global attenuation number as provided by conventional CT.^10–12We evaluated the capabilities of a photon counting spectral CT scanner to differentiate between the different components of coronary artery atherosclerotic plaque based on differences in spectral attenuation and iodine-based contrast agent maps.     

Intra-Individual,Inter-Vendor Comparison of Diffusion-Weighted MR Imaging of Upper Abdominal Organs at 3.0 Tesla with an Emphasis on the Value of Normalization with the Spleen

Objective

To compare the apparent diffusion coefficient (ADC) values of upper abdominal organs with 2 different 3.0 tesla MR systems and to investigate the usefulness of normalization using the spleen.

Materials and Methods

Forty-one patients were enrolled in this prospective study, of which, 35 patients (M:F, 27:8; mean age ± standard deviation, 62.3 ± 12.3 years) were finally analyzed. In addition to the routine liver MR protocol, single-shot spin-echo echo-planar diffusion-weighted imaging using b values of 0, 50, 400, and 800 s/mm² in 2 different MR systems was performed. ADC values of the liver, spleen, pancreas, kidney and liver lesion (if present) were measured and analyzed. ADC values of the spleen were used for normalization. The Pearson correlation, Spearman correlation, paired sample t test, Wilcoxon signed rank test and Bland-Altman method were used for statistical analysis.

Results

For all anatomical regions and liver lesions, both non-normalized and normalized ADC values from 2 different MR systems showed significant correlations (r = 0.5196–0.8488). Non-normalized ADC values of both MR systems differed significantly in all anatomical regions and liver lesions (p < 0.001). However, the normalized ADC of all anatomical regions and liver lesions did not differ significantly (p = 0.065–0.661), with significantly lower coefficient of variance than that of non-normalized ADC (p < 0.009).

Conclusion

Normalization of the abdominal ADC values using the spleen as a reference organ reduces differences between different MR systems, and could facilitate consistent use of ADC as an imaging biomarker for multi-center or longitudinal studies.