32البقرة :

Whole Body MRI Versus Whole Body MRI Versus 99m99m Tc-Tc-Methylene Diphosphonate Methylene Diphosphonate

Scintigraphy In Detection Of Scintigraphy In Detection Of Skeletal MetastasesSkeletal Metastases

Prof. Mervat ShafikProf. Mervat Shafik Head of Radiology Department Head of Radiology Department

Cairo UniversityCairo University

Prof. Moharram El BadawiProf. Moharram El Badawi Head of Radiology DepartmentHead of Radiology Department

NCI Cairo UniversityNCI Cairo University

Presented byPresented by

Osama Anwer Osama Anwer RaslanRaslan

Supervised bySupervised by

Ass. Prof. Walid SolimanAss. Prof. Walid Soliman Head of Nuclear Medicine Head of Nuclear Medicine

DepartmentDepartmentNCI Cairo UniversityNCI Cairo University

Metastases are by far the Metastases are by far the commonest malignant commonest malignant bone tumourbone tumour, outnumbering many times primary , outnumbering many times primary bone tumours. bone tumours.

99mTc-Phosphonate-based skeletal scintigraphy is 99mTc-Phosphonate-based skeletal scintigraphy is the standard method for the initial staging of bone the standard method for the initial staging of bone metastasesmetastases

It depicts bone metastases at a relatively It depicts bone metastases at a relatively advanced advanced

stagestage of tumor infiltration when osteoblastic host of tumor infiltration when osteoblastic host reaction to tumor deposits has already occurred. reaction to tumor deposits has already occurred.

It has limited anatomic detail, sensitivity and It has limited anatomic detail, sensitivity and specificityspecificity

Recent advances in hardware technology, Recent advances in hardware technology, the introduction of the introduction of fast MR sequencesfast MR sequences, , non-non-invasivenessinvasiveness, , lack of radiationlack of radiation and high and high diagnostic accuracy diagnostic accuracy renewed the interest inrenewed the interest in using WB-MRI in detection of skeletal using WB-MRI in detection of skeletal metastases.metastases.

It was proved that, MRI was superior to It was proved that, MRI was superior to scintigraphy in respect of scintigraphy in respect of sensitivity (92% sensitivity (92% vs. 58%)vs. 58%) and and specificity (97% vs. 85%).specificity (97% vs. 85%). (Layer (Layer et al, 1994)et al, 1994)..

Bone metastasis can be classified into Bone metastasis can be classified into fourfour types, namely, types, namely, osteolytic, osteoblastic, mixed, osteolytic, osteoblastic, mixed, or intertrabecular type.or intertrabecular type.

Carcinomas of the Carcinomas of the breast, prostate, and lungbreast, prostate, and lung, , in decreasing order, are the in decreasing order, are the commoncommon sources sources of skeletal metastases in a general population.of skeletal metastases in a general population.

Skeletal metastases predominantly affect the Skeletal metastases predominantly affect the axial skeletonaxial skeleton, a region rich in , a region rich in red marrow red marrow asas it it has large has large capillary networkcapillary network, a , a sluggish blood sluggish blood flowflow, and the , and the suitable tissuesuitable tissue for growth of for growth of tumour embolitumour emboli..

T1w-images T2w-images FSE-IR&STIR images

Yellow Marrow

Bright(Isointense to subcutaneous

fat)

Less Bright Black

Red Marrow Intermediate(Between

subcutaneous fat & muscle)

Moderately high(Slightly

brighter than muscles)

Allow discrimination between red marrow & Pathology

which will have a higher signal

Cancellous &Cortical

bone

Signal Void

99m99m Tc-MDP uptakeTc-MDP uptake is is greatest the axial skeletongreatest the axial skeleton, , with relatively less intense with relatively less intense uptake in extremities and uptake in extremities and skullskull

Background activity is Background activity is normally seen in normally seen in soft tissuessoft tissues

kidneyskidneys are routinely are routinely visualized in visualized in normalnormal subjects subjects and should have and should have less less intensity than the adjacent intensity than the adjacent lumbar spinelumbar spine

Body coverage was Body coverage was achieved using a achieved using a maximum of maximum of four four overlapping coronaloverlapping coronal body coil acquisitions.body coil acquisitions.

11stst Station: From the Station: From the head to upper chesthead to upper chest

22ndnd Station: Rest of Station: Rest of chest till upper pelvischest till upper pelvis

33rdrd Station: Rest of Station: Rest of pelvis till kneepelvis till knee

44thth Station: Knee to Station: Knee to ToesToes

The The spinespine was was imaged in imaged in 2 2 overlapped sagittaloverlapped sagittal stations using the stations using the CTL CTL coilcoil

11stst station: cervical & station: cervical & upper dorsal.upper dorsal.

22ndnd station: lower station: lower dorsal till sacraldorsal till sacral

Position of the Position of the upper extremitiesupper extremities was was dictated by dictated by patient’s habituspatient’s habitus, in large , in large patients, the patients, the arms arms were placed were placed above the above the headhead, requiring an , requiring an additional coronaladditional coronal acquisition.acquisition.

Total Total aquision time 28:00aquision time 28:00 minutes, extended to minutes, extended to 30:50 minutes if the extra coronal station for upper 30:50 minutes if the extra coronal station for upper limb was donelimb was done

The patients The patients in/out timein/out time ranged from 36-42 min ranged from 36-42 min with an average time of with an average time of 39 39 min.min.

There are There are two options to obtain the hard copytwo options to obtain the hard copy::

Printing the images which showed the Printing the images which showed the pathologypathology: : in the in the routine wayroutine way, or , or after matchingafter matching. The average . The average number of films was number of films was 4 to 6 4 to 6 films.films.

Printing Printing allall the images: average of the images: average of 99 films. films.

Of the Of the 2323 patients patients 1515 were were femalesfemales and and 88 malesmales

YoungestYoungest was was 3939 years and the years and the oldest oldest 7878 years, years, meanmean age was age was 53 53 yearsyears

Males35%

Females65%

Regarding the Regarding the 1ry 1ry , most of the , most of the patients came with patients came with breast cancerbreast cancer followed by followed by bladder cancerbladder cancer, , and and prostatic prostatic carcinomacarcinoma

1ry malignant tumor

No. Of case

Breast 12

Prostate 3

Bladder 4

Thyroid 1

HCC 1

Lung cancer 1

Nasopharengyal 1

Data Analyses based on Patient-Data Analyses based on Patient-by-Patient Comparisonby-Patient Comparison

3 / 233 / 23 patients were patients were concordantlyconcordantly found to be found to be totally totally freefree by both WB-MRI & BS, leaving by both WB-MRI & BS, leaving 2020 patients which patients which was analyzed as follows:was analyzed as follows:

WB-MRI: -WB-MRI: - 1515 / 20 / 20 had had skeletal metastasesskeletal metastases, , 55 had had benignbenign findings and findings and nono patients were found to be patients were found to be uncertainuncertain..

BS: -BS: - 11 / 2011 / 20 had had skeletal metastasesskeletal metastases, , 22 had had benign benign findings, and findings, and 77 patients were found to be patients were found to be uncertainuncertain necessitating further investigationsnecessitating further investigations

Data Analyses based on Region-by-Data Analyses based on Region-by-Region ComparisonRegion Comparison

78 / 25378 / 253 regions were regions were metastaticmetastatic, , 175 / 253175 / 253 regions were regions were freefree of of metastases (including regions diagnosed as benign or uncertain).metastases (including regions diagnosed as benign or uncertain).

WB-MRI:WB-MRI: Discovered Discovered 73 / 78 metastatic73 / 78 metastatic regions, with a regions, with a sensitivity 93.5%sensitivity 93.5%

and and PPV 100%PPV 100% 180180 areas to be areas to be freefree of metastases, with of metastases, with 5 false negative5 false negative areas, areas,

making its making its specificity 100%specificity 100% & & NPV 97.2%,NPV 97.2%, its its accuracy 98%accuracy 98%

BS :BS : Discovered Discovered 45 / 78 metastatic45 / 78 metastatic regions, and regions, and 2 falsely positive 2 falsely positive

regionsregions, with a , with a sensitivity 57.6%sensitivity 57.6% and and PPV 95.7%PPV 95.7% 206 206 areas to be areas to be freefree of metastases, with of metastases, with 31 false negative31 false negative areas, areas,

making its making its specificity 98.8%specificity 98.8% & & NPV 83.4%NPV 83.4% its its accuracy 86.1%accuracy 86.1%

WB-MRIWB-MRI clearly surpassed BS at clearly surpassed BS at spine, pelvis and both extremitiesspine, pelvis and both extremities, , respectively. WB-MRI was slightly respectively. WB-MRI was slightly better at the better at the sternumsternum

BS BS was better than WB-MRI at the was better than WB-MRI at the ribs and shoulderribs and shoulder

BothBoth modalities were equal at the modalities were equal at the skullskull

Data Analyses based on Number of Data Analyses based on Number of LesionsLesions

Total numberTotal number of lesions detected by of lesions detected by WB-WB-MRI (183 / 196 lesion) MRI (183 / 196 lesion) , with a , with a sensitivity sensitivity 93.5%93.5% , compared to , compared to 82 / 19682 / 196 lesions lesions detected by detected by BSBS, with a , with a sensitivity 41.8%sensitivity 41.8%

It also It also confirmedconfirmed the higher sensitivity of the higher sensitivity of WB-MRI WB-MRI in the in the spine, pelvis & extremitiesspine, pelvis & extremities, in , in addition to the addition to the skull and shoulderskull and shoulder..

PPV PPV of of WB-MRI 100%WB-MRI 100% , & that of , & that of BS BS 96.4%96.4%

Extraskeletal LesionsExtraskeletal Lesions

WB-MRIWB-MRI elucidated elucidated 59 59 tumor relatedtumor related extraskeletal extraskeletal lesionslesions, including 5 1ry detection, 1 chest wall , including 5 1ry detection, 1 chest wall recurrence in breast cancer, 2 cases with bilateral recurrence in breast cancer, 2 cases with bilateral lung metastases not discovered beforelung metastases not discovered before

BSBS only detected only detected 2 tumor related extraskeletal 2 tumor related extraskeletal lesionslesions, which were bilateral hydronephrotic , which were bilateral hydronephrotic changes complicating bladder cancerchanges complicating bladder cancer

WB-MRIWB-MRI detected detected 35 35 tumor non relatedtumor non related extraskeletal lesionsextraskeletal lesions, the most serious of which , the most serious of which was hydronephrotic changes, plural effusionswas hydronephrotic changes, plural effusions

Case 1Case 1

53 y, male, with 53 y, male, with Papillary thyroid Papillary thyroid carcinomacarcinoma complaining of sudden onset complaining of sudden onset

of of paraplegiaparaplegia

Impact on Management:Impact on Management:

Patient was sent for urgent Patient was sent for urgent surgical surgical decompressiondecompression procedure. procedure.

Case 2Case 2

64 y , Male, with 64 y , Male, with prostatic adenocarcinomaprostatic adenocarcinoma, , complaining of generalized complaining of generalized bone achesbone aches

and multiple and multiple enlarged lymph nodesenlarged lymph nodes..

Biopsy from cervical lymph Biopsy from cervical lymph node:node:

Diffuse Large Cell Non-Hodgkin Lymphoma

Impact on Management:Impact on Management:

Patient was diagnosed with a Patient was diagnosed with a second second primaryprimary of Lymphoma. of Lymphoma.

CaseCase 3 3

45 y, female , with 45 y, female , with TCCTCC of the urinary of the urinary bladderbladder

Impact on Management: Impact on Management:

Patient was diagnosed with Patient was diagnosed with vertebral and vertebral and lung metastaseslung metastases, for which she received , for which she received radiotherapy on the cervical and lumber radiotherapy on the cervical and lumber

spine and chemotherapy for lung spine and chemotherapy for lung metastases.metastases.

Case 4Case 4

50 y, female patient, with 50 y, female patient, with IDCIDC of the left of the left breast.breast.

Impact on Management:Impact on Management:

In addition to the chemotherapy, patient In addition to the chemotherapy, patient was referred to the was referred to the radiotherapyradiotherapy

department for management of the department for management of the spinalspinal lesions.lesions.

Case 5Case 5

Male , 78 y , with Male , 78 y , with prostatic prostatic adenocarcinomaadenocarcinoma

Impact on Management:Impact on Management:

Took chemotherapy for Took chemotherapy for bone & lungbone & lung lesion lesion in addition to radiotherapy on in addition to radiotherapy on

symptomatic and weight baring areassymptomatic and weight baring areas

Case 6Case 6

66 y, male patient, 66 y, male patient, HCCHCC, complaining of , complaining of numbness numbness of both lower limbs and low of both lower limbs and low

back pain.back pain.

Impact on Management: Impact on Management:

Skeletal Skeletal metastases were ruled metastases were ruled outout, and patient was sent for , and patient was sent for Neuro-surgical consultationNeuro-surgical consultation

Case 7Case 7

57 y, female , with 57 y, female , with metastatic breast cancer metastatic breast cancer to the brain and lungsto the brain and lungs, complaining from , complaining from acute onset of acute onset of paraplegia with sensory paraplegia with sensory

level at D8level at D8

Impact on Management:Impact on Management:

Patient received radiotherapy on the Patient received radiotherapy on the spinal spinal cord metastasescord metastases in addition to in addition to prophylactic on the femoral.prophylactic on the femoral.

X-rayX-ray requires loss of up to requires loss of up to 50 %50 % of bone of bone mineral content to detect mineral content to detect osteolytic osteolytic lesionslesions, , and minimum of and minimum of 30%30% increase in increase in bone mineral bone mineral to appreciate scleroticto appreciate sclerotic lesions, making it of lesions, making it of limited value in earlylimited value in early detection of skeletal metastases. detection of skeletal metastases.

CTCT cannot cannot distinguish red from fattydistinguish red from fatty marrow, marrow, diffuse & symmetricdiffuse & symmetric Infiltrating Infiltrating marrow neoplasms & suffer from marrow neoplasms & suffer from beam beam hardening & streak artifactshardening & streak artifacts, so CT is , so CT is restrictedrestricted in studying marrow disorder in studying marrow disorder..

BSBS can image the whole body with can image the whole body with reasonable reasonable sensitivitysensitivity at a at a acceptable cost and timeacceptable cost and time, so it , so it remained the method of choice in screening for remained the method of choice in screening for bone metastases. However, bone metastases. However, it lacked specificity it lacked specificity requiring further imaging in many casesrequiring further imaging in many cases

The well established The well established high contrast and spatial high contrast and spatial resolution of MRIresolution of MRI in imaging in imaging bone marrowbone marrow & soft & soft tissuetissue and the introduction of and the introduction of new fastnew fast sequences, which is available in most sequences, which is available in most commercially used machines, paved the way for commercially used machines, paved the way for the innovation of WB-MRIthe innovation of WB-MRI

Using Using WB-MRIWB-MRI, an , an excellent overviewexcellent overview of the skeletal of the skeletal system was obtained system was obtained in all 23 casesin all 23 cases, results showed that it , results showed that it had had higher overall sensitivity, specificity and accuracy than higher overall sensitivity, specificity and accuracy than BSBS, as it could detect , as it could detect all of the 15 metastatic casesall of the 15 metastatic cases, while , while BSBS characterized only 11 cases characterized only 11 cases. .

WB-MRIWB-MRI was superior to BS at : spine ( was superior to BS at : spine (1919 > regions), lower > regions), lower limbs & pelvis (limbs & pelvis (33 > regions), upper limb ( > regions), upper limb (44 >regions) & >regions) & sternum (sternum (11 > region). > region). BSBS was superior at the ribs and was superior at the ribs and shoulder (shoulder (11 > region), while > region), while both both were equal at the skull.were equal at the skull.

The The pathological basispathological basis of these findings : Since cellular of these findings : Since cellular bone marrow is the initial site of metastatic seeding to bone marrow is the initial site of metastatic seeding to bone, MRI can detect metastatic lesions at an early stage, bone, MRI can detect metastatic lesions at an early stage, before changes of the bone metabolism occur that make before changes of the bone metabolism occur that make lesions detectable on bone scan. lesions detectable on bone scan. (Algra et al, 1991).(Algra et al, 1991).

• BSBS diagnosed diagnosed 7 cases as uncertain7 cases as uncertain, , which were successfully reveled to be which were successfully reveled to be 4 4 metastatic and 3 benign cases by WB-MRImetastatic and 3 benign cases by WB-MRI. . On the other hand On the other hand nono cases were cases were diagnosed as diagnosed as uncertain by WB-MRIuncertain by WB-MRI

•In addition, In addition, WB-MRIWB-MRI found an found an extra 78 extra 78 benign skeletal lesionsbenign skeletal lesions including, including, degenerative disc prolepses with or degenerative disc prolepses with or without cord compressions, sever without cord compressions, sever osteoporotic changes with and without osteoporotic changes with and without vertebral compression collapsevertebral compression collapse

Our technique was also able to elucidate Our technique was also able to elucidate 59 tumor-related 59 tumor-related extra skeletal manifestationsextra skeletal manifestations (e.g. metastatic lung deposits (e.g. metastatic lung deposits not discovered before) ,and not discovered before) ,and 35 non-tumor related35 non-tumor related findings findings (e.g. pleural effusion).(e.g. pleural effusion).

Whatever the malignancy, MRI represents the most Whatever the malignancy, MRI represents the most appropriate method of staging in unfortunate patients appropriate method of staging in unfortunate patients affected affected during pregnancy during pregnancy (Eustace et al., 1999)(Eustace et al., 1999)

It is our believe that WB-MRI is an It is our believe that WB-MRI is an acceptable alternativeacceptable alternative to Bone scintigraphy to Bone scintigraphy , , possible indicationspossible indications includes: includes:

1)When ever BS is not feasible:1)When ever BS is not feasible:

a)a) When ever BS is When ever BS is not availablenot available

b)b) In In chronic renal failurechronic renal failure, which result in sub optimal , which result in sub optimal scintigraphy & subject patient to high radiationscintigraphy & subject patient to high radiation

c)c) in a in a pregnant femalepregnant female. WB-MRI is safe, non-ionizing, . WB-MRI is safe, non-ionizing, non-invasive. Till now there is no solid proof that MRI non-invasive. Till now there is no solid proof that MRI would endanger the outcome of pregnancy.would endanger the outcome of pregnancy.

2) solitary increased uptake detected 2) solitary increased uptake detected in BS:in BS:

WB-MRI can effectively diagnose the nature WB-MRI can effectively diagnose the nature of these lesions by either of these lesions by either

a) detecting more lesions a) detecting more lesions reveling the multiple reveling the multiple naturenature of the pathology of the pathology

b) detecting b) detecting tumifactive behaviortumifactive behavior such as soft such as soft tissue componentstissue components

c) reviling other c) reviling other extra skeletal tumor extra skeletal tumor metastasesmetastases

3) Cases with Suspected Spinal 3) Cases with Suspected Spinal Metastases: Metastases:

• WB-MRI WB-MRI more sensitive, specific and accuratemore sensitive, specific and accurate than BS in spinethan BS in spine

• able differentiate able differentiate malignant from benign malignant from benign collapsecollapse

• demonstrate demonstrate post-metastatic sequelaepost-metastatic sequelae of of vertebral metastases (e.g. cord compression)vertebral metastases (e.g. cord compression)

•shows shows metastatic foci else weremetastatic foci else were in the skeleton in the skeleton

4) Cases with Suspected Pelvic 4) Cases with Suspected Pelvic Metastases:Metastases:

WB-MRI showed WB-MRI showed more lesionsmore lesions in this in this region than BSregion than BS

able to able to differentiate between benign differentiate between benign and metastatic lesionsand metastatic lesions (e.g. hip (e.g. hip effusion)effusion)

5) Cases with Suspected Lower 5) Cases with Suspected Lower Limb Metastases:Limb Metastases:

lower limbs are a lower limbs are a weight bearing areaweight bearing area, which , which when subjected to stress may lead to when subjected to stress may lead to pathological fracturepathological fracture..

In addition to being In addition to being more sensitive and more sensitive and specificspecific

WB-MRI can WB-MRI can provide the clinician with a direct provide the clinician with a direct viewview of the affected parts, thus aiding them in of the affected parts, thus aiding them in planning for prophylactic radiotherapy or planning for prophylactic radiotherapy or surgery surgery

WB-MRI is the optimal screening tool for skeletal WB-MRI is the optimal screening tool for skeletal metastases as:metastases as:

It is more sensitive and specific than BSIt is more sensitive and specific than BSAllows direct visualization of large volume of bone marrow (aid in Allows direct visualization of large volume of bone marrow (aid in planning of prophylactic radiotherapy)planning of prophylactic radiotherapy)Earlier detection of skeletal metastases Earlier detection of skeletal metastases Non invasive Non invasive No radiation hazardsNo radiation hazardsNo contrast complicationsNo contrast complicationsOnly safe method for pregnant patientsOnly safe method for pregnant patientsWell suited for almost any situation whether it is solitary or diffuse Well suited for almost any situation whether it is solitary or diffuse extensive metastasesextensive metastasesDetect extra skeletal lesions (e.g. hepatic & pulmonary metastases)Detect extra skeletal lesions (e.g. hepatic & pulmonary metastases)Detect tumor related complications. (e.g. cord compression)Detect tumor related complications. (e.g. cord compression)

We believe that advances in MRI technology, skill of interpretation & We believe that advances in MRI technology, skill of interpretation & further studies in that direction would help in further exploitation of this further studies in that direction would help in further exploitation of this technique as the technique as the optimum screening technique for cancer patients, optimum screening technique for cancer patients, saving time, money &staff effortsaving time, money &staff effort