Jonathan I. Gear

Development of patient-specific molecular imaging phantoms using a 3D printer

PURPOSE The aim of the study was to investigate rapid prototyping technology for the production of patient-specific, cost-effective liquid fillable phantoms directly from patient CT data. METHODS Liver, spleen, and kidney volumes were segmented from patient CT data. Each organ was converted to a shell and filling holes and leg supports were added using computer aided design software and prepared for printing. Additional fixtures were added to the liver to allow lesion inserts to be fixed within the structure. Phantoms were printed from an ultraviolet curable photopolymer using polyjet technology on an Objet EDEN 500V 3D printer. RESULTS The final print material is a clear solid acrylic plastic which is watertight, rigid, and sufficiently durable to withstand multiple assembly and scanning protocols. Initial scans of the phantoms have been performed with Tc-99m SPECT and F-18 PET/CT. CONCLUSIONS The organ geometry showed good correspondence with anatomical references. The methodology developed can be generally applied to other anatomical or geometrical phantoms for molecular imaging.

The conflict between treatment optimization and registration of radiopharmaceuticals with fixed activity posology in oncological nuclear medicine therapy

The new European Council Directive 2013/59 (http://eur-lex. europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX: 32013L0059&from=EN), to be translated into national legislations before 6 February 2018, in article 56 (Optimisation) states: BFor all medical exposure of patients for radiotherapeutic purposes, exposures of target volumes shall be individually planned and their delivery appropriately verified, taking into account that doses to non-target volumes and tissues shall be as low as reasonably achievable and consistent with the intended radiotherapeutic purpose of the exposure^. No doubt this statement holds for nuclear medicine therapy, since in article 4 of the same, directive definition 81 states that Bradiotherapeutic^ means pertaining to radiotherapy, including nuclear medicine for therapeutic purposes. The directive thus asks for dosimetry, as is routinely implemented in radiotherapy, using external beam or brachytherapy sources. However, in nuclear medicine therapy, absorbed dose planning is rarely performed. One of the main reasons is the amount of work needed for internal dosimetry that includes multiple whole-body counts or scintigraphy and sometimes blood samples over some days after administration. The Bintended purpose^ in all therapeutic exposures is treatment efficacy against malignant disease. The optimization principle (as low as reasonably achievable, ALARA) of article 56, when applied in a therapy situation, states that absorbed doses to nontarget tissues should be kept reasonably low, but not so low as to lose efficacy. We think that this applies above all to the fight against life-threatening cancer. As a consequence, we believe that to adhere to the optimization principle in oncological patients, nuclear medicine therapy should be based on individualized dosimetry.

From fixed activities to personalized treatments in radionuclide therapy: lost in translation?

We read with interest the letter by Giammarile et al. [1] addressing our editorial in which we proposed that the European Medicines Agency should allow the option of a dosimetrybased approach to the treatment of cancer with radionuclide therapy [2]. Our editorial was intended to draw attention to the potential legal issues of recommending an approach to treatment that could contravene the European Council Directive 2013/59 [3] and national legislation, as the directive (article 56) states that “For all medical exposure of patients for radiotherapeutic purposes, exposures of target volumes shall be individually planned and their delivery appropriately verified...”. This directive is intended to “lay down basic safety standards for the protection of dangers arising from exposure to ionizing radiation” and emphasizes the need for ‘justification’ and ‘optimization’ of intentional radiation exposures of patients. We do not agree with the conclusion of this letter that cancer therapy with radiopharmaceuticals should be developed “in a similar manner to chemotherapeutics^, “independent of tumor load and metastases^ and is “better characterized as a tumor-selective treatment modality with more similarities to systemic chemotherapy”. In any scientific field concerned with biological effects of radiation, whether for therapy or radiation protection purposes, the effects of radiation on tissue are primarily dependent on the well-established measure absorbed dose. Consequently, great efforts are made to calculate absorbed doses in cells, tissues, and organs. The hypothesis that the level of activity administered has a greater impact on treatment outcome than the subsequent biodistribution, the radiation delivery and the absorbed dose is ignoring the results of decades of radiation research on biological systems.

Objective comparison of lesion detectability in low and medium-energy collimator iodine-123 mIBG images using a channelized Hotelling observer

Abstract Iodine-123 mIBG imaging is widely regarded as a gold standard for diagnostic studies of neuroblastoma and adult neuroendocrine cancer although the optimal collimator for tumour imaging remains undetermined. Low-energy (LE) high-resolution (HR) collimators provide superior spatial resolution. However due to septal penetration of high-energy photons these provide poorer contrast than medium-energy (ME) general-purpose (GP) collimators. LEGP collimators improve count sensitivity. The aim of this study was to objectively compare the lesion detection efficiency of each collimator to determine the optimal collimator for diagnostic imaging. The septal penetration and sensitivity of each collimator was assessed. Planar images of the patient abdomen were simulated with static scans of a Liqui-Phil™ anthropomorphic phantom with lesion-shaped inserts, acquired with LE and ME collimators on 3 different manufacturers’ gamma camera systems (Skylight (Philips), Intevo (Siemens) and Discovery (GE)). Two-hundred normal and 200 single-lesion abnormal images were created for each collimator. A channelized Hotelling observer (CHO) was developed and validated to score the images for the likelihood of an abnormality. The areas under receiver-operator characteristic (ROC) curves, Az, created from the scores were used to quantify lesion detectability. The CHO ROC curves for the LEHR collimators were inferior to the GP curves for all cameras. The LEHR collimators resulted in statistically significantly smaller Azs (p  <  0.05), of on average 0.891  ±  0.004, than for the MEGP collimators, 0.933  ±  0.004. In conclusion, the reduced background provided by MEGP collimators improved 123I mIBG image lesion detectability over LEHR collimators that provided better spatial resolution.

EANM practical guidance on uncertainty analysis for molecular radiotherapy absorbed dose calculations

A framework is proposed for modelling the uncertainty in the measurement processes constituting the dosimetry chain that are involved in internal absorbed dose calculations. The starting point is the basic model for absorbed dose in a site of interest as the product of the cumulated activity and a dose factor. In turn, the cumulated activity is given by the area under a time–activity curve derived from a time sequence of activity values. Each activity value is obtained in terms of a count rate, a calibration factor and a recovery coefficient (a correction for partial volume effects). The method to determine the recovery coefficient and the dose factor, both of which are dependent on the size of the volume of interest (VOI), are described. Consideration is given to propagating estimates of the quantities concerned and their associated uncertainties through the dosimetry chain to obtain an estimate of mean absorbed dose in the VOI and its associated uncertainty. This approach is demonstrated in a clinical example.

Inter-comparison of quantitative imaging of lutetium-177 (177Lu) in European hospitals

BackgroundThis inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (177Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems.Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources—they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source.ResultsThe volumes reported by the participants for the inner section of the source were all within 29% of the true value and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value.ConclusionsA variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods.