a prospective study conducted at our hospital involved 41 pregnant women who bore a total of 41 fetuses and visited our department for level - ii obstetric us . gestational age ranged from 12 to 37 ( mean , 25 ) weeks : for nine , it was 10 - 20 weeks ; for 23 , 21 - 30 weeks ; and for the remaining nine , more than 30 weeks . among these 41 women , the findings of fetal us were normal in 31 and abnormal in the remaining ten . abnormalities included facial cleft ( 2 ) , echogenic thoracic mass ( 2 ) , diaphragmatic hernia ( 1 ) , omphalocele ( 1 ) , duodenal atresia ( 1 ) , echogenic bowel ( 1 ) and dilatation of the renal pelvis ( 2 ) . the diagnosis was confirmed at delivery or autopsy in five of these ten patients , two were followed - up for five months , and the remaining three were lost to follow - up . in two fetuses with a dilated renal pelvis , postnatal renal us findings were normal . all images were obtained using a 2 - 5 mhz convex transducer ( hdi 5000 ; advanced technology laboratories , bothell , wash . cus was used first , followed , successively , by thi and pihi , and for each technique , standard institutional us protocols were applied and between 20 and 30 images were obtained ; in each instance , the same depth , magnification and focus were used , and gray - scale gain was adjusted to optimize image quality . all cus , thi , and pihi images obtained were evaluated by two radiologists using a 22k picture archiving and communication system monitor ( general electric medical systems integrated imaging solutions , mt . one or two representative images for each of six organ systems , namely the brain , spine , heart , abdomen , extremities and face , were selected for review ( table 1 ) . after reviewing the given standard planes obtained using the three techniques , the overall conspicuity of each organ system was subjectively assigned one of four grades ( 4 - excellent , 3 - good , 2 - fair , or 1- poor ) , depending on the definition of borders and internal structures . the grades were averaged between the readers , and cus , thi , and pihi were compared . during the review , each reader in the ten fetuses whose us findings were abnormal , the conspicuity of these anomalies was graded by one radiologist , using the same system . grades for the three different techniques were then compared . for multiple statistical comparison between the three techniques , friedman 's test was used ; a p value of less than 0.05 was considered statistically significant . to establish interobserver agreement , individual data sets from the two readers were compared . cus , thi and pihi were quantified using their weighted kappa value , with a 95-percent confidence interval . a comparison of overall conspicuity and definition of the borders and internal structures of the six organ systems , as seen at cus , thi , and pihi , appears in table 2 . for the brain , heart , abdomen and face , the overall conspicuity of fetal organs was significantly better at thi and pihi than at cus ( fig . 1 ) ( p < 0.05 ) , though there was no significant difference between thi and pihi . for the spine ( fig . in two first - trimester fetuses , thi and pihi delineated internal structures better than cus ( fig . in the ten abnormal fetuses , the abnormality was more clearly delineated at both thi and pihi than at cus ( p < 0.05 ) ( table 3 ) . this was so , for example , for a body - wall defect and a liver - containing sac in the fetus with omphalocele . the dilated renal pelvis present in two fetuses was clearly depicted using all three techniques , though soft - tissue contrast was slightly better and the near - field artifact was smaller at thi and pihi than at cus ( fig . 4 ) . in the two fetuses with echogenic thoracic masses , the lesions contrasted better with surrounding normal lung at thi and pihi than at cus . in the two fetuses with a facial cleft , the lesions were clearer at thi and pihi than at cus . the overall kappa value was 0.845 ( very good agreement ) , with a 95 percent confidence interval of 0.831 - 0.888 . for the three techniques , all kappa values calculated ranged between 0.711 and 1.000 ( table 4 ) . a comparison of overall conspicuity and definition of the borders and internal structures of the six organ systems , as seen at cus , thi , and pihi , appears in table 2 . for the brain , heart , abdomen and face , the overall conspicuity of fetal organs was significantly better at thi and pihi than at cus ( fig . 1 ) ( p < 0.05 ) , though there was no significant difference between thi and pihi . for the spine ( fig . in two first - trimester fetuses , thi and pihi delineated internal structures better than cus ( fig . in the ten abnormal fetuses , the abnormality was more clearly delineated at both thi and pihi than at cus ( p < 0.05 ) ( table 3 ) . this was so , for example , for a body - wall defect and a liver - containing sac in the fetus with omphalocele . the dilated renal pelvis present in two fetuses was clearly depicted using all three techniques , though soft - tissue contrast was slightly better and the near - field artifact was smaller at thi and pihi than at cus ( fig . 4 ) . in the two fetuses with echogenic thoracic masses , the lesions contrasted better with surrounding normal lung at thi and pihi than at cus . in the two fetuses with a facial cleft , the lesions were clearer at thi and pihi than at cus . the overall kappa value was 0.845 ( very good agreement ) , with a 95 percent confidence interval of 0.831 - 0.888 . for the three techniques , all kappa values calculated ranged between 0.711 and 1.000 ( table 4 ) . owing to the presence of a natural sonic window of amniotic fluid , us is the most suitable modality for the diagnosis of fetal abnormalities , and its safety and availability have facilitated its wide use in nearly all pregnancies . cus is , however , of limited utility for the evaluation of obese patients and those with poly- or oligohydramnios , uterine anomalies , or multiple myomas ( 20 - 21 ) . thi is a us technique in which the us beamformer transmits at one frequency and the transducer receives at twice that frequency ( harmonic frequency ) . using a filter to process the received signal , only the returning second harmonic signal is used to produce the image . the use of a narrow us beam width provides better lateral resolution and improved depiction of the details of small anatomic structures ( 24 - 25 ) . additionally , because of the smaller dynamic range involved , tissue contrast resolution is accentuated , and since nonlinear propagation causing waveform distortion and the diffraction effect is less , thi produces fewer artifacts than cus ( 25 ) . pihi is a newer technique free of the bandwidth limitation of thi ( 9 ) . by transmitting two mirror - imaged pulses of alternating phases , the fundamental signals are cancelled out , generating a pure harmonic signal ( 26 ) , and very high spatial resolution is known to result . while thi uses a narrow receiving filter , pihi uses broader transmitting and receiving bandwidths , and resolution is thus improved ( 24 ) . the well - known disadvantages of pihi are its slow frame rate and flashing artifacts , though in fetal imaging these do not seem to often cause problems . soft tissues , including the skin , subcutaneous tissue and musculature , seem to be more conspicuous at thi than at cus . in our study , thi and pihi were superior to cus for the brain , heart , and abdomen , but pihi was better than cus for evaluation of the face . in contrast , bony structures were not clearly delineated at thi or pihi ; they were more often obscured by clear posterior sonic shadowing of bones than at cus ( fig . 2 ) , a fact which may explain the lower grades of conspicuity seen at thi and pihi of the spine and extremities . for these areas , there were no statistically significant differences between the three techniques . the conspicuity of all six organ systems and overall image quality were similar at pihi and at thi , though among the three techniques , near - field artifacts in fetal brain beneath the calvarium and in fetal abdomen beneath the abdominal wall were smallest at pihi ( fig . published reports have not addressed the question of the safety of thi and pihi in fetal imaging . although egerton et al . ( 27 ) reported possible increases in tissue temperature during harmonic imaging , thi and pihi without contrast appear , in theory , to be safe in an ordinary clinical setting . thi obtains weak harmonic signals generated in the body , and except for the selection of a narrower bandwidth frequency , the transmitted sound beam remains the same as with cus . pihi uses two sound pulses per scan line , resulting in more sound energy per line ; as the frame rate is halved , however , average sound energy over time is the same . for this reason , both the thermal and mechanical indices encountered in clinical practice , using either technique , usually remain the same as with cus . interobserver agreement in our study was very good , with close correlation between the findings of the two reviewers , an overall weighted kappa value of 0.845 , and a 95-percent confidence range of 0.831 - 0.888 . there was very close agreement ( 0.711 - 1.000 of the weighted kappa value ) between the two observers for both normal and abnormal fetuses , and all six organ systems . this result demonstrates , we believe , that both thi and pihi are consistently superior to cus and can thus serve as useful tools for imaging of the fetus . first , since the image characteristics of the three different techniques were recognizably different , the readers were not blinded , during their analysis , to which had been employed . second , we included in this study only patients who visited our department for level - ii fetal us , and for this reason , the gestational age of the fetuses varied , and was not well controlled . fetal imaging findings are strongly influenced by gestational age , and our thi and pihi findings may , for this reason , have been affected . third , only ten abnormal fetuses were studied , and to determine the usefulness of these techniques and the applicability of our findings , further investigation by means of a well - designed prospective study is warranted . in conclusion , both thi and pihi are superior to cus for the evaluation of normal and abnormal fetuses , particularly for assessment of the brain , heart , abdomen , and face . because it provides high tissue contrast resolution and artifacts are fewer , harmonic imaging may be particularly useful in the evaluation of internal fetal organs .