99mTc thyroid imaging system using multiple imaging plates

A system for taking static thyroid ^99mTc images was devised by using multiple imaging plates (IPs) and a low-energy high resolution collimator. System spatial resolution of the IP systems and the gamma camera was determined by referring to standards set by the National Electrical Manufacturers Association. Sensitivity was represented by using lower detection limits (LDLs). The sensitivity and resolution of IP systems using 16 IP probes connecting two collimators and 9 IPs were determined by using a 20 ml thyroid phantom, and compared with the sensitivity of gamma cameras. The sensitivity of the IP systems increased in proportion to the number of IPs. The sensitivity and resolution of a probe using 6 IPs and a high resolution collimator were equivalent to or superior to the gamma camera for taking static thyroid ^99mTc images. IP systems can be applied clinically as mobile static nuclear imaging devices. The performance of IP systems should be thoroughly investigated for combinations of various collimators and the number of IPs in order to verify their efficacy for imaging all organs.     

Intraoperative gamma imaging of axillary sentinel lymph nodes in breast cancer patients

Sentinel lymph node (SLN) biopsy is now standard practice in the management of many breast cancer patients. Localization protocols vary in complexity and rates of success. The least complex involve only intraoperative gamma counting of radiotracer uptake or intraoperative visualization of blue-dye uptake; the most complex involve preoperative gamma imaging, intraoperative counting and intraoperative dye visualization. Intraoperative gamma imaging may improve some protocols. This study was conducted to obtain preliminary experience and information regarding intraoperative imaging. Sixteen patients were enrolled: 8 in a protocol that included intraoperative counting and dye visualization (probe/dye), 8 in a protocol that involved intraoperative imaging, counting and dye visualization (camera/probe/dye). Preoperative imaging of all 16 patients was performed using a GE 500 gamma camera with a LEAP collimator (300 cpm/μCi). The results of this imaging were not, however, given to the surgeon until the surgeon had completed the procedures required for the study. A Care Wise C-Trak probe was used for intraoperative counting. A Gamma Medica Inc. GammaCAM/OR (12.5 × 12.5 cm FOV) with a LEHR collimator (135 cpm/μCi) was used for intraoperative imaging. Times from start of surgery to external detection of a radioactive focus and to completion of excision of SLNs were recorded. Foci were detected preoperatively via imaging in 16/16 patients. Intraoperative external detection using the probe was accomplished in less than 4 min (mean = 1.5 min) in 15/16 patients, and via intraoperative imaging in 6/8 patients. The average time for completion of excision of nodes was 19 min for probe/dye and 28 min for camera/probe/dye. In one probe/dye case, review of the preoperative images prompted the surgeon to resume axillary dissection and remove one additional SLN.     

Quantitative evaluation of scintillation camera imaging characteristics of isotopes used in liver radioembolization

Background

Scintillation camera imaging is used for treatment planning and post-treatment dosimetry in liver radioembolization (RE). In yttrium-90 (90Y) RE, scintigraphic images of technetium-99m (99mTc) are used for treatment planning, while 90Y Bremsstrahlung images are used for post-treatment dosimetry. In holmium-166 (166Ho) RE, scintigraphic images of 166Ho can be used for both treatment planning and post-treatment dosimetry. The aim of this study is to quantitatively evaluate and compare the imaging characteristics of these three isotopes, in order that imaging protocols can be optimized and RE studies with varying isotopes can be compared.

Methodology/Principal Findings

Phantom experiments were performed in line with NEMA guidelines to assess the spatial resolution, sensitivity, count rate linearity, and contrast recovery of 99mTc, 90Y and 166Ho. In addition, Monte Carlo simulations were performed to obtain detailed information about the history of detected photons. The results showed that the use of a broad energy window and the high-energy collimator gave optimal combination of sensitivity, spatial resolution, and primary photon fraction for 90Y Bremsstrahlung imaging, although differences with the medium-energy collimator were small. For 166Ho, the high-energy collimator also slightly outperformed the medium-energy collimator. In comparison with 99mTc, the image quality of both 90Y and 166Ho is degraded by a lower spatial resolution, a lower sensitivity, and larger scatter and collimator penetration fractions.

Conclusions/Significance

The quantitative evaluation of the scintillation camera characteristics presented in this study helps to optimize acquisition parameters and supports future analysis of clinical comparisons between RE studies.     

An analysis of an alternative scintimammography system

A novel system for scintimammography has been developed, which has high spatial resolution, good sensitivity, better energy resolution, and lower cost than conventional systems. In addition, the system incorporates the potential to provide additional information and functionality beyond imaging, including x,y and z lesion location, integration with a stereotatic biopsy system and images both breasts at the same time. Methods: The system uses sheet NaI (Tl) crystals, PM Tubes, and slant hole collimators allowing complete separation of the breast from the chest wall while remaining in contact with the breast at all depths. The physical characteristics are presented, with images and compared with other systems. Results: The limit of lesion detectability in terms lesion size, depth and contrast has been investigated and compared with a current conventional system. Using accepted patient dose data, the anticipated radiopharmaceutical activity related to the lesion size is used for imaging tests and provides a measure of expected of lesion detectability. Conclusion: Large area, sheet NaI (Tl) detector systems with slant hole collimators are capable of imaging features of below 5mm size at both surface and at clinical depths with the amount of activity expected in lesions of this size with patient administered doses in the clinically acceptable range.     

Design and development of a dedicated portable gamma camera system for intra-operative imaging

PurposeWe developed a high performance portable gamma camera platform dedicated to identification of sentinel lymph nodes (SLNs) and radio-guided surgery for cancer patients. In this work, we present the performance characteristics of SURGEOSIGHT-I, the first version of this platform that can intra-operatively provide high-resolution images of the surveyed areas.MethodsAt the heart of this camera, there is a 43 × 43 array of pixelated sodium-activated cesium iodide (CsI(Na)) scintillation crystal with 1 × 1 mm² pixel size and 5 mm thickness coupled to a Hamamatsu H8500 flat-panel multi-anode (64 channels) photomultiplier tube. The probe is equipped with a hexagonal parallel-hole lead collimator with 1.2 mm holes. The detector, collimator, and the associated front-end electronics are encapsulated in a common housing referred to as head.ResultsOur results show a count rate of ∼41 kcps for 20% count loss. The extrinsic energy resolution was measured as 20.6% at 140 keV. The spatial resolution and the sensitivity of the system on the collimator surface was measured as 2.2 mm and 142 cps/MBq, respectively. In addition, the integral and differential uniformity, after uniformity correction, in useful field-of-view (UFOV) were measured 4.5% and 4.6%, respectively.ConclusionsThis system can be used for a number of clinical applications including SLN biopsy and radiopharmaceutical-guided surgery.     

La caméra à semi-conducteur D-Spect : aspects techniques et applications cliniques

Clinical practice in nuclear medicine has largely changed in the last decade, particularly with the arrival of PET/CT and SPECT/CT. New semiconductor cameras could represent the next evolution in our nuclear medicine practice. Due to the resolution and sensitivity improvement, this technology authorizes fast speed acquisitions, high contrast and resolution images performed with low activity injection. The dedicated cardiology D-Spect camera (Spectrum Dynamics, Israel) is based on semiconductor technology and provides an original system for collimation and images reconstruction. We describe here our clinical experience in using the D-Spect with a preliminary study comparing D-DPECT and conventional gamma camera.     

Assessing good operating conditions for intraoperative imaging of melanoma sentinel nodes by a portable gamma camera

ObjectiveTo provide guidance for reliable identification of low-activity sentinel nodes in the setting of melanoma surgery using a commercial hand-held gamma camera.MethodsThe average uptake of ^99mTc nanocolloid by sentinel nodes was evaluated in 95 excised nodes using a Sentinella 102^® (Oncovision, Valencia, Spain) portable gamma camera. The device sensitivity was assessed for different source depths and collimator distances, imaging an 8-mm sphere filled with a known-activity solution of ^99mTc. Five nuclear medicine physicians were asked to identify the source at different activity levels and positions within the field of view. For each image the number of signal counts inside a circular region of interest (ROI) was measured, while the variability of ROI counts among operators was assessed. The number of counts providing a minimal, near-constant inter-operator variability was determined as a criterion for a consistent identification of the source. Either the minimum activity or the acquisition time needed to collect the appropriate statistics were then calculated.ResultsThe median SN uptake (0.5%) turned out to be compatible with values reported in the literature. The sensitivity of the compact gamma camera ranged from ∼25 cpm/kBq to ∼1 cpm/kBq. A total of 50 counts in the ROI circumscribing the lymph node-simulating sphere appeared to be a robust criterion for identification of the source.ConclusionsTen megabecquerels of injected activity at the time of surgery and one minute of acquisition allows reliable identification of sentinel nodes for collimator-to-source distances up to 10 cm.     

The 18 kDa translocator protein (peripheral benzodiazepine receptor) expression in the bone of normal, osteoprotegerin or low calcium diet treated mice

The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195.In vitro, the TSPO is highly expressed in osteoblastic and osteoclastic cells.In situ, constitutive expression of TSPO is found in bone marrow and trabecular bone, e.g., spongiosa. Mice with a reduction of bone turnover induced by a 4-day treatment of osteoprotegerin reduces [(3)H]PK11195 binding in the spongiosa (320±128 Bq x mg(-1), 499±106 Bq x mg(-1) in saline-treated controls). In contrast, mice with an increase in bone turnover caused by a 4-day low calcium diet increases [(3)H]PK11195 binding in the spongiosa (615±90 Bq x mg(-1)). Further, our study includes technical feasibility data on [(18)F]fluoride microPET imaging of rodent bone with altered turnover. Despite [(18)F]fluoride having high uptake, the in vivo signal differences were small. Using a phantom model, we describe the spillover effect and partial volume loss that affect the quantitative microPET imaging of the small bone structures in experimental mouse models. In summary, we demonstrate the expression of TSPO in small rodent bone tissues, including osteoblasts and osteoclasts. A trend increase in TSPO expression was observed in the spongiosa from low to high bone turnover conditions. However, despite the potential utility of TSPO expression as an in vivo biomarker of bone turnover in experimental rodent models, our small animal PET imaging data using [(18)F]fluoride show that even under the condition of a good biological signal-to-noise ratio and high tracer uptake, the currently achievable instrument sensitivity and spatial resolution is unlikely to be sufficient to detect subtle differences in small structures, such as mouse bone.     

188Re image performance assessment using small animal multi-pinhole SPECT/PET/CT system

PurposeThe goal of this study was to investigate the performance of a pre-clinical SPECT/PET/CT system for ¹⁸⁸Re imaging.MethodsPhantom experiments were performed aiming to assess the characteristics of two multi-pinhole collimators: ultra-high resolution collimator (UHRC) and high-energy ultra high resolution collimator (HE-URHC) for imaging ¹⁸⁸Re. The spatial resolution, image contrast and contrast-to-noise ratio (CNR) were investigated using micro-Jaszczak phantoms. Additionally, the quantification accuracy of ¹⁸⁸Re images was evaluated using two custom-designed phantoms. The ¹⁸⁸Re images were compared to those obtained with ^99mTc (gold standard); the acquired energy spectra were analyzed and Monte-Carlo simulations of the UHRC were performed. To verify our findings, a C57BL/6-mouse was injected with ¹⁸⁸Re-microspheres and scanned with both collimators.ResultsThe spatial resolution achieved in ¹⁸⁸Re images was comparable to that of ^99mTc. Acquisitions using HE-UHRC yielded ¹⁸⁸Re images with higher contrast and CNR than UHRC. Studies of quantitative accuracy of ¹⁸⁸Re images resulted in <10% errors for both collimators when the activity was calculated within a small VOI around the object of interest. Similar quantification accuracy was achieved for ^99mTc. However, ¹⁸⁸Re images showed much higher levels of noise in the background. Monte-Carlo simulations showed that ¹⁸⁸Re imaging with UHRC is severely affected by down-scattered photons from high-energy emissions. The mouse images showed similar biodistribution of ¹⁸⁸Re-microspheres for both collimators.ConclusionsVECTor/CT provided ¹⁸⁸Re images quantitatively accurate and with quality comparable to ^99mTc. However, due to large penetration of UHRC by high-energy photons, the use of the HE-UHRC for imaging ¹⁸⁸Re in VECTor/CT is recommended.     

A GSO positron/single-photon imaging detector

We have developed and tested a GSO position sensitive gamma detector which can be used with positron and single-photon radionuclides for imaging breast cancer or sentinel lymph node detection. Because GSO has a relatively good energy resolution for annihilation gammas as well as low energy gamma photons, and does not contain any natural radioisotopes it can be used for positron imaging and lower energy single-photon imaging. The imaging detector consists of a GSO block, 2-inch square multichannel position sensitive photo-multiplier tube (PSPMT), and associated electronics. For the positron imaging, coincidence between the imaging detector and a single gamma probe is measured. For the single-photon imaging, a tungsten collimator is mounted in front of the imaging detector. With this configuration, it was possible to image both positron radionuclides and low energyu single-photon radionuclides.     

Magnetoacoustic imaging of electrical conductivity of biological tissues at a spatial resolution better than 2 mm

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an emerging approach for noninvasively imaging electrical impedance properties of biological tissues. The MAT-MI imaging system measures ultrasound waves generated by the Lorentz force, having been induced by magnetic stimulation, which is related to the electrical conductivity distribution in tissue samples. MAT-MI promises to provide fine spatial resolution for biological tissue imaging as compared to ultrasound resolution. In the present study, we first estimated the imaging spatial resolution by calculating the full width at half maximum (FWHM) of the system point spread function (PSF). The actual spatial resolution of our MAT-MI system was experimentally determined to be 1.51 mm by a parallel-line-source phantom with Rayleigh criterion. Reconstructed images made from tissue-mimicking gel phantoms, as well as animal tissue samples, were consistent with the morphological structures of the samples. The electrical conductivity value of the samples was determined directly by a calibrated four-electrode system. It has been demonstrated that MAT-MI is able to image the electrical impedance properties of biological tissues with better than 2 mm spatial resolution. These results suggest the potential of MAT-MI for application to early detection of small-size diseased tissues (e.g. small breast cancer).     

CdTe compact gamma camera for coded aperture imaging in radioguided surgery

The aim of this work was to assess the performance of a prototype compact gamma camera (MediPROBE) based on a CdTe semiconductor hybrid pixel detector, for coded aperture imaging. This probe can be adopted for various tasks in nuclear medicine such as preoperative sentinel lymph node localization, breast imaging with ^99mTc radiotracers and thyroid imaging, and in general in radioguided surgery tasks. The hybrid detector is an assembly of a 1-mm thick CdTe semiconductor detector bump-bonded to a photon-counting CMOS readout circuit of the Medipix2 series or energy-sensitive Timepix detector. MediPROBE was equipped with a set of two coded aperture masks with 0.07-mm or 0.08-mm diameter holes. We performed laboratory measurements of field of view, system spatial resolution, and signal-difference-to-noise ratio, by using gamma-emitting radioactive sources (¹⁰⁹Cd, ¹²⁵I, ²⁴¹Am, ^99mTc). The system spatial resolution in the lateral direction was 0.56 mm FWHM (coded aperture mask with holes of 0.08 mm and a 60 keV source) at a source-collimator distance of 50 mm and a field of view of 40 mm by side. Correspondingly, the longitudinal resolution in 3D source localization tasks was about 3 mm. MediPROBE showed a significant improvement in terms of spatial resolution when equipped with the high-resolution coded apertures, with respect to the performance previously reported with 1–2 mm pinhole apertures as well as with respect to adopting a 0.35 mm pinhole aperture.     

High resolution scintimammography helps in differentiating benign from malignant findings in scintigraphic hot spots

Several efforts have been focusing on the development of detectors devoted to high solution ^99mTc sestamibi scintimammography to improve sensitivity for non palpable lesions. To this aim new high resolution scintillation gamma camera was developed under the “Integiated Mammographic Imaging” project. The gamma camera, made by CAEN and Pol.Hi.Tech, has an overall dimension of 112×120×75mm3. It consists of an array of 1 in. PSPMTs Hamamatsu H8520-C12 closely packed, a NaI(T1) scintillation array (1.8×1.8×6mm³ pixel) and a general purpose collimator. By this gamma camera a clinical experience on a few patients with breast cancer suspicion was performed. In this paper we show how high resolution approach allows to better categorize the lesions on the basis of the morphology of the spatial distribution of the radiotracer in the breast tissue. By comparing conventional and high resolution images of a young patient (29 y.o.) with breast cancer suspicion, it appears clear how the Anger, camera images showed a defined hot spot, highly suggestive of malignant lesion; on the contrary, the high resolution scan shown a large and inhomogeneous uptake area with the absence of clear and focal character of the uptake, to be considered as a probably non malignant lesions. This resuh was confirmed by byoptical findings that diagnosed the echographic findings as a benign inflammatory lesion.     

Nuclear magnetic resonance microscopy ofAncistrocladus heyneanus

Summary The tropical lianaAncistrocladus heyneanus, which is known for its biologically active naphthylisoquinoline alkaloids, has been studied by nuclear magnetic resonance (NMR) microscopy for the first time. The spatial resolution of the cross-sectional NMR images was of the order of 20 m. Quantitative NMR relaxation time images of the root and the shoot show great contrast between different tissue regions. In addition, we observed the regional distribution of chemical compounds inAncistrocladus heyneanus by chemical-shift NMR microscopy. The NMR imaging results were compared with light and fluorescence microscopic images and reveal the excellent tissue characterization using NMR technology.Abbreviations NMR nuclear magnetic resonance - CSI chemical-shift magnetic resonance imaging - FOV field of view - TE echo time - TR repetition time     

Determinations of catechols in small volumes of plasma using ion-pair reversed phase liquid chromatography/electrochemistry

A method with improved sensitivity for detection of catechols (CA) in small volumes of plasma using an ion-pair reversed phase HPLC system with electromechemical detection is presented. Fast isocratic separations were obtained by using 7.5 cm x 4.6 mm (i.d.) reversed phase columns with 3C18 3 micron silica particles. The CA:s L-DOPA, Noradrenaline (NA), Adrenaline (A), Dihydroxybenzylamine (DHBA, i.s.), DOPAC and Dopamine (DA) were separated in less than 4 min. The performance of three different electrochemical cells was compared with respect to hydrodynamic voltammogram, band broadening effect, linearity and detection limit. The sample preparation procedure using alumina extraction of CA:s, was modified to improve recoveries and decrease dilution factors. A modified carbon paste cell (CP-O) gave a response 4-8 times higher than what is previously reported for GC cells. Detection limits were: L-DOPA 80, NA 1.25, A 1.25, DHBA 0.4, DOPAC 1.25 and DA 0.6 pg/injection. Application to plasma from rat and fish (cod) under rest, exercise and stress is reported. The method allows determination of CA:s in small volumes of plasma (less than 500 microliter) obtained several times a day from the same animal even if it is small (less than 1/2 kg), is under rest and parts of the plasma sample are to be used for analysis of other parameters than CA:s.     

N.m.r. imaging of intact biological systems

Internal images of structured objects may be obtained with n.m.r. by labelling component parts with different magnetic field strengths and therefore recognizably different n.m.r. frequencies. A linear field gradient generates a one-dimensional projection of nuclear density and a variety of techniques are employed to manipulate this one-dimensional probe to yield internal images in two and three dimensions. In the past few years, n.m.r. imaging, sometimes also called zeugmatography or spin mapping, has been applied progressively to provide proton images of small phantoms, fruit, vegetables and small animals, and finally to in vivo imaging of the human body; it promises to provide a valuable means of interior investigation of intact biological systems generally. For medical imaging the method is non-invasive, does not use ionizing radiations, appears to be without hazard and penetrates bony cavities without attenuation. Furthermore, other n.m.r. parameters, for example, relaxation times and fluid flow, may also be mapped; there is evidence that the relaxation times from tumours are significantly longer than those from corresponding normal tissue. Effort to date has mostly been concentrated on proton n.m.r., but some work has been done with other nuclei. Three examples are shown of n.m.r. images of intact biological systems: a fruit, an animal and a human system. The discussion includes the quantitative nature of the images, tissue discrimination, the relation between the resolution in the image and image acquisition time, attenuation and phase shift of the r.f. field in the biological tissue, and magnets suitable for n.m.r. imaging. In principle, all conventional n.m.r. techniques can be combined with n.m.r. methods in order to investigate heterogeneous systems. Overhauser imaging is briefly discussed.     

1064 nm acoustic resolution photoacoustic microscopy

Photoacoustic imaging is a noninvasive imaging technique having the advantages of high‐optical contrast and good acoustic resolution at improved imaging depths. Light transport in biological tissues is mainly characterized by strong optical scattering and absorption. Photoacoustic microscopy is capable of achieving high‐resolution images at greater depth compared to conventional optical microscopy methods. In this work, we have developed a high‐resolution, acoustic resolution photoacoustic microscopy (AR‐PAM) system in the near infra‐red (NIR) window II (NIR‐II, eg, 1064 nm) for deep tissue imaging. Higher imaging depth is achieved as the tissue scattering at 1064 nm is lesser compared to visible or near infrared window‐I (NIR‐I). Our developed system can provide a lateral resolution of 130 μm, axial resolution of 57 μm, and image up to 11 mm deep in biological tissues. This 1064‐AR‐PAM system was used for imaging sentinel lymph node and the lymph vessel in rat. Urinary bladder of rat filled with black ink was also imaged to validate the feasibility of the developed system to study deeply seated organs.      

Lesion radioactivity concentration estimation using dual modality gamma ray/X-ray imaging

Although the use of dedicated gamma cameras in scintimammography permits closer access to the breast and improved spatial resolution relative to conventional gamma cameras, the task of quantifying the radiotracer concentration in the lesion relative to that in the surrounding breast tissue remains challenging because of the lesion-depth-dependent effects of attenuation and collimator blur. We are developing a dual modality scanner that combines digital x-ray mammography and a dedicated gamma camera on a common upright gantry. Here we present the results of a phantom study evaluating the use of the dual modality system for quantifying radioactivity in breast lesions. In addition to assessment of lesion activity, lesion volume estimates are necessary to quantify lesion radioactivity concentration. We have used multiple view x-ray imaging as a means of estimating lesion volume. Using phantom experiments, we have empirically derived a formula for correction of the measured z dimension of the lesion. The error obtained in quantification of lesion activity is approximately 10%. Lesion volume can be assessed with an accuracy comparable to that of lesion activity assessment using five x-ray views. These results suggest that the error in lesion concentration assessment is approximately 14%.     

Noise properties of reconstructed images in a kilo-voltage on-board imaging system with iterative reconstruction techniques: A phantom study

X-ray computed tomography (CT) images obtained with a kilo-voltage (kV) on-board imaging (OBI) system improve the accuracy of patient setup and treatment planning. The use of iterative reconstruction techniques (IRTs) for CT imaging can also reduce radiation dose compared to analytic reconstruction techniques. Despite these improvements, the image quality varies with IRTs, and the noise structure of reconstructed images can be distorted by IRTs. In this study, the noise properties and spatial resolution of the images reconstructed by IRTs were evaluated in terms of conventional noise metrics, high-order statistics, noise spectral density (NSD) and modulation transfer function (MTF) at different radiation doses. A kV OBI system mounted on a Varian Trilogy machine and a CATPHAN600 phantom were used to obtain projections, and the projections were reconstructed by Feldkamp (FDK), algebraic reconstruction technique (ART), maximum-likelihood expectation–maximization (MLEM) and total variation (TV) minimization algorithms. The reconstructed images were compared according to mean, standard deviation, skewness, kurtosis, NSD and MTF at different radiation doses. The results demonstrated that the noise properties and spatial resolution of reconstructed images depend on the type of IRT and the radiation dose. The noise structures are altered by IRTs and can be characterized by high-order statistics and NSD, as well as conventional noise metrics. In conclusion, high-order statistics and NSD should be considered in order to provide detailed information for the images reconstructed by IRTs. Also, trade-off among noise properties, spatial resolution and contrast is important to optimize image quality obtained using IRTs.     

Magnetic resonance imaging using a clinical whole body system: an introduction to a useful technique in small animal experiments.

A clinical whole body magnetic resonance imaging (MRI) system with high resolution coils was used to obtain non-invasive images of the living rat. The results demonstrate the feasibility of the set-up and the advantages of this new imaging technique: detailed information, no extra costs, longitudinal studies without killing animals and simple anaesthesia. It is concluded that in small animal experimentation, this use of high resolution coils in whole body magnetic resonance systems may be particularly helpful in establishing effects of experimental procedures. Whenever non-invasive visualization is required, especially in longitudinal animal studies, e.g. biomaterial research or tumour investigation, this use of MRI will offer challenging possibilities.