Improved geometric accuracy of whole body diffusion-weighted imaging at 1.5T and 3T using reverse polarity gradients.

Whole body diffusion-weighted imaging (WB-DWI) is increasingly used in oncological applications, but suffers from misalignments due to susceptibility-induced geometric distortion. As such, DWI and structural images acquired in the same scan session are not geometrically aligned, leading to difficulties in e.g. lesion detection and segmentation. In this work we assess the performance of the reverse polarity gradient (RPG) method for correction of WB-DWI geometric distortion. Multi-station DWI and structural magnetic resonance imaging (MRI) data of healthy controls were acquired at 1.5T (n = 20) and 3T (n = 20). DWI data was distortion corrected using the RPG method based on b = 0 s/mm2 (b0) and b = 50 s/mm2 (b50) DWI acquisitions. Mutual information  (MI) between low b-value DWI and structural data increased with distortion correction (P < 0.05), while improvements in region of interest (ROI) based similarity metrics, comparing the position of incidental findings on DWI and structural data, were location dependent. Small numerical differences between non-corrected and distortion corrected apparent diffusion coefficient (ADC) values were measured. Visually, the distortion correction improved spine alignment at station borders, but introduced registration-based artefacts mainly for the spleen and kidneys. Overall, the RPG distortion correction gave an improved geometric accuracy for WB-DWI data acquired at 1.5T and 3T. The b0- and b50-based distortion corrections had a very similar performance.

18F-FDG-PET/MRI in preoperative staging of oesophageal and gastroesophageal junctional cancer.

AIM: To evaluate integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/magnetic resonance imaging (MRI), in comparison with the standard technique, integrated 18F-FDG-PET/computed tomography (CT), in preoperative staging of oesophageal or gastroesophageal junctional cancer. MATERIALS AND METHODS: In the preoperative staging of 16 patients with oesophageal or gastroesophageal junctional cancer, 18F-FDG-PET/MRI was performed immediately following the clinically indicated 18F-FDG-PET/CT. MRI-sequences included T1-weighted fat-water separation (Dixon's technique), T2-weighted, diffusion-weighted imaging (DWI), and gadolinium contrast-enhanced T1-weighted three-dimensional (3D) imaging. PET was performed with 18F-FDG. Two separate teams of radiologists conducted structured blinded readings of 18F-FDG-PET/MRI or 18F-FDG-PET/CT, which were then compared regarding tumour measurements and characteristics as well as assessment of inter-rater agreement (Cohen's kappa) for the clinical tumour, nodal and metastatic (TNM) stage. RESULTS: There were no medical complications. Comparison of tumour measurements revealed high correlations without significant differences between modalities. The maximum standardised uptake value (SUVmax) values of the primary tumour with 18F-FDG-PET/MRI had excellent correlation to those of 18F-FDG-PET/CT (0.912, Spearman's rho). Inter-rater agreement between the techniques regarding T-stage was only fair (Cohen's kappa, 0.333), arguably owing to relative over-classification of the T-stage using 18F-FDG-PET/CT. Agreements in the assessment of N- and M-stage were substantial (Cohen's kappa, 0.849 and 0.871 respectively). CONCLUSION: Preoperative staging with 18F-FDG-PET/MRI is safe and promising with the potential to enhance tissue resolution in the area of interest. 18F-FDG-PET/MRI and 18F-FDG-PET/CT correlated well for most of the measured values and discrepancies were seen mainly in the assessment of the T-stage. These results facilitate further studies investigating the role of 18F-FDG-PET/MRI in, e.g., predicting or determining the response to neoadjuvant therapy.

Validation of 3 T MRI including diffusion-weighted imaging for nodal staging of newly diagnosed intermediate- and high-risk prostate cancer.

AIM: To prospectively validate 3 T magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) for preoperative lymph node (LN) staging in a clinical setting, in intermediate- and high-risk prostate cancer (PCa) patients using laparoscopic extended LN dissection (ePLND) as the reference standard. MATERIALS AND METHODS: Between August 2011 and May 2013, 40 newly diagnosed intermediate and high-risk PCa patients underwent preoperative LN staging with 3 T MRI DWI using histopathology of ePLND as the reference standard. The sensitivity, specificity, and accuracy of MRI DWI were calculated. A subgroup analysis of proven LN-positive patients was made to investigate differences in PSA, Gleason score, number, and size of LN metastases, estimated risk of LN involvement, and if curative treatment was indicated, between the true-positive and the false-negative groups. RESULTS: A total of 728 LN were harvested from six anatomical regions per patient (external, obturator, internal) with a mean number of 18 LNs per patient (range 11-40). Twenty patients had histologically proven LN-positive disease. MRI DWI was true positive in 11 patients, false negative in nine patients, false positive in two patients, and true negative in 18 patients, resulting in 90% specificity, 55% sensitivity, and 72.5% accuracy. The true-positive patients had significantly more involved LNs (mean 6.9 versus 2.7, p=0.017), with larger diameter (mean 12.3 versus 5.2 mm, p=0.048) and fewer were treated with curative intent (six versus nine, p=0.03), compared with the false-negative group. CONCLUSION: MRI DWI LN staging has a low sensitivity but high specificity. The true-positive patients have a considerably higher burden of LN metastases compared to false-negative patients.

Whole-body diffusion-weighted MRI and (18)F-FDG PET/CT can discriminate between different lymphoma subtypes.

AIM: To determine whether combined 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron-emission tomography (PET)/computed tomography (CT) and diffusion-weighted imaging (DWI) can be used for characterisation of different lymphoma subtypes, i.e., indolent versus aggressive lymphoma, and also to assess the prognostic value of different quantitative parameters of whole-body (WB) DWI and (18)F-FDG PET/CT. MATERIALS AND METHODS: Pre-therapeutic WB magnetic resonance imaging (MRI) including DWI and (18)F-FDG PET/CT were performed in lymphoma patients. Different quantitative DWI and (18)F-FDG PET/CT parameters were evaluated for characterisation of different lymphoma subtypes. These parameters were also correlated, both separately and in combination, against overall survival (OS) and progression-free survival (PFS). A lesion-by-lesion analysis was performed for correlation analysis between maximum standardised uptake value (SUVmax), mean standardised uptake value (SUVmean) and mean apparent diffusion coefficient (ADC). RESULTS: Fifty patients were included in the study and divided into three groups: Hodgkin's lymphoma (HL), n=12; aggressive non-Hodgkin's lymphoma (NHL), n=29 (including 20 patients with diffuse large B-cell lymphoma, DLBCL); and indolent NHL, n=9. Indolent NHL showed significantly lower mean ADC values than the other two lymphoma groups (p=0.013). Aggressive NHL had a higher SUVmax than HL. The OS analysis of all patients showed a relationship (p=0.006) between increased mean ADC and longer OS. A model with both SUVmean and mean ADC, strengthened the possibility to predict PFS; however, a separate analysis of the DLBCL patients showed that none of the quantitative parameters could predict OS or PFS. CONCLUSION: ADC can discriminate between indolent and aggressive NHL. This finding can be useful in assessing possible transformation from indolent to aggressive NHL. ADC, ADC/SUV, and SUV cannot predict OS/PFS independent of lymphoma subtype.

Comparison between MRI and CT in prediction of peritoneal carcinomatosis index (PCI) in patients undergoing cytoreductive surgery in relation to the experience of the radiologist.

BACKGROUND: To compare CT and MRI for peritoneal carcinomatosis index (PCI) assessment and to compare assessments made by the radiologist based on their experiences. METHOD AND MATERIALS: MRI and CT of abdomen and pelvis were performed on 39 prospectively followed by surgery directly. Two blinded radiologists with different experience levels evaluated PCI separately on different occasions on 19 cases initially and later on the remaining 20. The agreement between the radiologists' assessment and surgical findings in total and per site were recorded. RESULTS: Total PCI: The experienced radiologist was able to assess total tumor burden correctly on both CT and MRI (kappa = 1.0). For the inexperienced radiologist the assessment was better on CT (kappa = 0.73) compared to MRI (kappa = 0.58). Different sites: The experienced radiologist showed high agreement with kappa = 0.77 for MRI and 0.80 for CT. Corresponding figures were 0.39 and 0.60 for the inexperienced radiologist. For the second phase the agreement levels increased for the inexperienced radiologist increased to 0.80 and 0.70, respectively. CONCLUSION: CT and MRI are equal when read by experienced radiologist. CT shows better results when read by an inexperienced radiologist compared to MRI, however the results of the latter can easily be improved.

Quantitative renal cortical perfusion in human subjects with magnetic resonance imaging using iron-oxide nanoparticles: influence of T1 shortening.

BACKGROUND: Using conventional contrast agents, the technique of quantitative perfusion by observing the transport of a bolus with magnetic resonance imaging (MRI) is limited to the brain due to extravascular leakage. PURPOSE: To perform quantitative perfusion measurements in humans with an intravascular contrast agent, and to estimate the influence of the T1 relaxivity of the contrast agent on the first-pass response. MATERIAL AND METHODS: Renal cortical perfusion was measured quantitatively in six patients with unilateral renal artery stenosis using a rapid gradient double-echo sequence in combination with an intravenous bolus injection of NC100150 Injection, an intravascular contrast agent based on iron-oxide nanoparticles. The influence of T1 relaxivity was measured by comparing perfusion results based on single- and double-echo data. RESULTS: The mean values of cortical blood flow, cortical blood volume, and mean transit time in the normal kidneys were measured to 339+/-60 ml/min/100 g, 41+/-8 ml/100 g, and 7.3+/-1.0 s, respectively, based on double-echo data. The corresponding results based on single-echo data, which are not compensated for the T1 relaxivity, were 254+/-47 ml/min/100 g, 27+/-3 ml/100 g, and 6+/-1.2 s, respectively. CONCLUSION: The use of a double-echo sequence enabled elimination of confounding T1 effects and consequent systematic underestimation of the perfusion.

Lipid mobilization following Roux-en-Y gastric bypass examined by magnetic resonance imaging and spectroscopy.

BACKGROUND: Recent developments of magnetic resonance imaging (MRI) and spectroscopy have made it possible to quantify lipid deposited in different tissues. To what extent an improvement of glucose tolerance shortly after Roux-en-Y gastric bypass surgery (RYGBP) is reflected in lipid levels in liver and skeletal muscle, markers of insulin resistance, has not been clarified. METHODS: Whole-body MRI and MR spectroscopy (MRS) of liver and muscle and measurements of biochemical markers of glucose and lipid metabolism were performed at baseline and 1, 6, and 12 months following surgery in seven morbidly obese women. Volumes of adipose tissue depots and liver and muscle lipids were assessed from the MRI/MRS data. RESULTS: At 1 month postoperatively, body mass index and visceral and subcutaneous adipose tissues were reduced by 9%, 26%, and 10%, respectively, whereas no reductions in intrahepatocellular or skeletal intramyocellular lipid concentrations were found. Free fatty acid and beta-hydroxybutyrate levels were elevated two- and sixfold, respectively; glucose and insulin levels were lowered, indicating increased insulin sensitivity. Further weight loss up to 1 year was associated with reductions in all investigated lipid depots investigated, with the exception of the intramyocellular compartment. CONCLUSION: RYGBP causes rapid lipid mobilization from visceral and subcutaneous adipose depots and enhanced free fatty acid flux to the liver. An exceptional disconnection between liver fat and insulin sensitivity occurs in the early dynamic phase after surgery. However, in the late phase, the energy restriction imposed by the surgical procedure also reduces the liver lipids, but not the intramyocellular lipids.

A total atherosclerotic score for whole-body MRA and its relation to traditional cardiovascular risk factors.

The aim of this study was to create a scoring system for whole-body magnetic resonance angiography (WBMRA) that allows estimation of atherosclerotic induced luminal narrowing, and determine whether the traditional cardiovascular (CV) risk factors included in the Framingham risk score (FRS) were related to this total atherosclerotic score (TAS) in an elderly population. A group of 306 subjects, aged 70, were recruited from the general population and underwent WBMRA in a 1.5-T scanner. Three-dimensional sequences were acquired after administration of one i.v. injection of 40 ml gadodiamide. The arterial tree was divided into five territories (carotid, aorta, renal, upper and lower leg) comprising 26 vessel segments, and assessed according to its degree of stenosis or occlusion. FRS correlated to TAS (r = 0.30, P < 0.0001), as well as to the atherosclerotic score for the five individual territories. Of the parameters included in the FRS, male gender (P < 0.0001), systolic blood pressure (P = 0.0002), cigarette pack-years (P = 0.0008) and HDL cholesterol (P = 0.008) contributed to the significance. A scoring system for WBMRA was created. The significant relation towards traditional CV risk factors indicates that the proposed scoring system could be of value for assessing atherosclerotically induced luminal narrowing.

Macrophage uptake of ultra-small iron oxide particles for magnetic resonance imaging in experimental acute cardiac transplant rejection.

PURPOSE: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2* magnetic resonance imaging (MRI) in a clinical 1.5T scanner. MATERIAL AND METHODS: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2* was calculated. RESULTS: No significant difference in change in T2* could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. CONCLUSION: In our rat model, measurements of T2* after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection.

Chemical-shift micro-imaging of subcutaneous lesions.

A chemical-shift imaging technique was used for the study of small subcutaneous lesions. This study concerns micro-imaging of two females suffering from a tenosynovial giant cell tumor and an epidermal cyst. High-resolution water, fat and chemical-shift artifact-free images were obtained on a whole-body MR unit (1.5 T) equipped with a 23-mm microscopy surface coil and standard gradients (23 mT/m). A significant improvement in signal-to-noise ratio was achieved by reducing the receiver bandwidth to values below +/-10 kHz. The image data sets were acquired with resolution 0.1 x 0.13 mm in the plane, slice thickness 0.5 mm and with acquisition time less than 3 min. Spatial resolution, fat suppression, image texture and edge delineation were improved on spectroscopic images compared with those on conventional MR images.

Effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on MR imaging of normal red bone marrow in breast cancer patients with focal bone metastases.

PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on normal red bone marrow MR imaging in breast cancer patients with focal bone metastases. MATERIAL AND METHODS: Fifteen breast cancer patients who were examined before and after chemotherapy with T1-weighted-SE and long echo-time inversion-recovery turbo-spin-echo (long TE IR-TSE) sequences in the thoracolumbar spine and pelvis were retrospectively studied. Nine of them received G-CSF therapy after the administration of each chemotherapy course. Of these 9 patients, the MR follow-ups were performed during G-CSF in 4 patients and after G-CSF therapy in 5 patients. Six patients did not receive G-CSF. Signal intensity (SI) changes in normal bone marrow were evaluated visually in all patients and quantitatively in 13 patients. RESULTS: In all 4 patients investigated during G-CSF therapy a diffuse, homogeneous SI increase on long TE IR-TSE was observed visually and quantitatively in initially normal bone marrow. This change obscured some focal lesions in 2 patients. No such SI change was visible after G-CSF therapy (p = 0.008) or in patients not receiving G-CSF. On T1-weighted images an SI decrease was found both during and after G-CSF therapy, but an increase occurred in patients not receiving G-CSF. CONCLUSION: G-CSF-supported chemotherapy can induce diffuse SI changes in normal red bone marrow on MR imaging. On long TE IR-TSE, the changes are visible during G-CSF treatment and can lead to misinterpretations in the response evaluation of bone metastases to therapy.

Diagnosis of a patient with oncogenic osteomalacia using a phosphate uptake bioassay of serum and magnetic resonance imaging.

A previously healthy man with no family history of fractures presented with muscle pain, back pain and height loss. Investigations revealed hypophosphataemia, phosphaturia, undetectable serum 1,25-dihydroxyvitamin D and severe osteomalacia on bone biopsy, suggestive of a diagnosis of oncogenic osteomalacia. Thorough physical examination did not locate a tumour. Support for the diagnosis was obtained by detection of phosphate uptake inhibitory activity in a blinded sample of the patient's serum using a renal cell bioassay. On the basis of detection of this bioactivity, a total body magnetic resonance (MR) examination was performed. A small tumour was located in the right leg. Removal of the tumour resulted in the rapid reversal of symptoms and the abnormal biochemistry typical of oncogenic osteomalacia. Inhibitory activity was also demonstrated using the bioassay in serum from two other patients with confirmed or presumptive oncogenic osteomalacia, but not in serum from two patients with hypophosphataemia of other origin. This is the first case to be reported in which the diagnosis of oncogenic osteomalacia was assisted by demonstration of inhibitory activity of the patient's serum in a renal cell phosphate bioassay that provided an impetus for total body MR imaging.

Spectroscopic imaging of bone marrow composition in vertebral bodies.

The proton spectroscopic imaging technique that uses read gradient during acquisition was used for the measurement of the proton spectra in the lumbar and thoracic part of the spine of a patient with breast cancer without known skeletal metastases. The bone marrow fat/water ratios were evaluated in the same location before and after chemotherapy treatment. The results were corrected for relaxation effects. The fat/water ratios showed a significant increase as a consequence of the bone marrow degradation process due to chemotherapy. The proposed spectroscopic imaging technique offers rapid acquisition of proton spectra from large volumes of the vertebral bodies.

Pre-clinical results with Clariscan (NC100150 Injection); experience from different disease models.

A superparamagnetic nanoparticle (NC100150 Injection) was investigated in two different animal models; renal perfusion in pigs and tumour imaging in mice. In the pig model, qualitative first-pass perfusion maps following a bolus injection of NC100150 Injection enabled good visualisation of hypoperfused regions of the renal cortex following partial ligation of the renal artery. High temporal resolution was found to be essential to accurately capture the first passage of the contrast agent through the kidney due to the very rapid blood flow in normal renal cortex. In the tumour model (LS174T cells implanted in nude mice), NC100150 Injection was found to cause a gradual (over 60 min) signal increase on T1-w images in part of the tumours which was attributed to contrast agent leakage from the vascular space to the extravascular space in areas of increased capillary permeability. This observation is consistent with previous reports on the molecular cut-off size for vascular extraction for this tumour cell line. The specific enhancement of tumour tissue suggest potential utility of NC100150 Injection as an angiogenesis marker.

Endoanal ultrasound or magnetic resonance imaging for preoperative assessment of anal fistula: a comparative study.

OBJECTIVE: To compare endoanal ultrasound (EUS) with a 10-MHz probe vs. bodycoil magnetic resonance imaging (MRI) in the preoperative evaluation of anal fistula. SUBJECTS AND METHODS: 23 patients with fistula in the anal region underwent preoperative 0.5 T bodycoil MRI and 10 MHz EUS which included probing in 6 patients. The results of the EUS and MRI were compared against the surgical findings as a reference method. RESULTS: In classification of the primary tract there was agreement between EUS and surgical findings in 14 (61%) and between MRI and surgery in 11 (48%). Concerning the presence of an internal opening the corresponding figures were 17 (74%) and 10 (43%) and in judging the presence of an extension or an abscess 15 (65%) vs. 11 (48%), respectively. In three out of eight patients with nonhealing or recurrence after surgery preoperative imaging had shown an extension and/or an abscess that was not identified by the surgeon. CONCLUSION: EUS, sometimes complemented with probing, is well comparable to bodycoil MRI in classifying and describing the topography of an anal fistula.

Residual mass in aggressive lymphoma--does size, measured by computed tomography, influence clinical outcome?

Residual masses are frequently found in patients with aggressive lymphomas, following therapy. A study was undertaken to determine whether initial tumour size, changes during treatment, or size of the residual mass could provide prognostic information. Computed tomography (CT) examinations were carried out before, midway and after completion of chemotherapy in 37 patients with aggressive lymphoma with residual mass after treatment. The tumours were measured for both the greatest diameter sizes and area. The size of the residual mass correlated with the tumour size at diagnosis. Neither a large tumour size before treatment nor a large residual mass after treatment correlated with an increase in rate of relapse. The initial tumour reduction (measured after completion of half of the planned chemotherapy) was less pronounced in relapsing patients compared to relapse-free patients. Using a cut-off level of 70% tumour reduction (measured after completion of half of the planned chemotherapy), 66% of patients with a tumour reduction of < 70% relapsed, compared with 22% (p < 0.05) in those with more marked tumour regression.

Gadolinium-enhanced magnetic resonance angiography, digital subtraction angiography and duplex of the iliac arteries compared with intra-arterial pressure gradient measurements.

PURPOSE: to compare gadolinium-enhanced magnetic resonance angiography (Gd-MRA), digital subtraction angiography (DSA) and duplex of the iliac arteries with intra-arterial pressure gradient measurement as the reference method. MATERIALS AND METHODS: Gd-MRA, DSA and duplex examinations of the iliac arteries were performed in 30 patients (60 arteries) with lower-limb arterial occlusive disease. In 29 arteries, pressure measurements were made (n=25) or the artery was found to be occluded on catheterisation (n=4). An aortofemoral peak systolic pressure gradient of 20 mmHg or more was regarded as haemodynamically significant. Stenoses with a diameter reduction of 50% or more on MRA or DSA, or an increase in peak systolic velocity greater than 150% (duplex) were considered significant. MRA examinations were evaluated by means of maximum intensity projections (MRA-MIP) and using source images and curved multiplanar reconstruction (MRA-MPR). RESULTS: the sensitivity (specificity) for a significant iliac artery stenosis were 81% (75%) for MRA-MIP, 76% (75%) for MRA-MPR, 86% (88%) for DSA, and 72% (88%) for duplex. CONCLUSION: with intra-arterial pressure measurements as the reference method, similar results were achieved with Gd-MRA, DSA and duplex concerning the detection of haemodynamically significant iliac artery stenoses. The use of source images and multiplanar reconstructions resulted in higher accuracy for the detection of occlusions.

Value of transsternal core biopsy in patients with a newly diagnosed mediastinal mass.

Histopathologic analysis of an anterior mediastinal mass of unknown origin is essential for treatment decision. Mediastinoscopy is the most common procedure performed to obtain biopsies, but general anaesthesia and hospitalization are necessary. The aim of this study was to evaluate whether transsternal core biopsies, an easy outpatient biopsy technique, could be an alternative to mediastinoscopy. A biopsy instrument that makes it possible to reach tumours hidden behind bone was used for transsternal CT-guided core biopsies in 21 patients with a newly diagnosed anterior mediastinal mass. No severe side effects were observed. In 19/21 (90%) patients the biopsies were diagnostic. In 2/21 patients additional biopsy techniques had to be used. In these two patients Hodgkin's disease was suspected in the first biopsy procedures. The diagnosis was confirmed by new core biopsies, from other parts of the tumour, not using a transsternal approach (transclavicular and parasternal, respectively). In addition, one mediastinoscopy was performed in a patient who was diagnosed with a non-Hodgkin's lymphoma but where more material was needed for lymphoma subclassification. It is concluded that CT-guided transsternal core biopsy is a clinically valuable method in patients with a newly diagnosed anterior mediastinal mass.

Evaluation of new sclerotic bone metastases in breast cancer patients during treatment.

PURPOSE: According to the World Health Organization (WHO) criteria for response of bone metastases to therapy, new lesions indicate progressive disease. We intended to prove that a new sclerotic lesion on conventional radiography may also be a sign of a positive therapeutic response in a previously undetectable lytic metastasis. MATERIAL AND METHODS: In a previous placebo-controlled clinical trial of clodronate (Ostac) therapy, 139 breast cancer patients with bone metastases underwent both conventional radiography and bone scan every 6 months for 2 years with 99mTc before and during clodronate treatment. WHO criteria were applied for therapy response evaluation. RESULTS: In 24 patients, 52 new sclerotic lesions observed during therapy were selected for re-evaluation of conventional radiographs and bone scans. In 8 of the 24 patients, 17 of 52 new sclerotic lesions (33%) had showed positive uptake on previous bone scans. These lesions were possibly misinterpreted as new when applying WHO criteria. CONCLUSION: For better assessment of new sclerotic lesions during treatment, more sensitive techniques, e.g. bone scan, are needed as a complement to conventional radiography.